Co-reporter:Takeru Ehara, Mikio Fujii, Machiko Ono, Hiroyuki Akita
Tetrahedron: Asymmetry 2010 Volume 21(Issue 4) pp:494-499
Publication Date(Web):16 March 2010
DOI:10.1016/j.tetasy.2010.02.014
The total synthesis of methyl β-d-vicenisaminide 1 has been achieved. In this approach, the synthesis of enantiomerically pure methyl (4R,5S)- and (4S,5R)-4-azido-5-hydroxy-2(E)-hexenoates 2 was established by enzymatic resolution of (±)-anti-5-acetoxy -4-azido-2(E)-hexenoate 4. Another stereogenic center was introduced by base-catalyzed intramolecular conjugate addition of a hemiacetal-derived alkoxide nucleophile obtained by the reaction of methyl (4S,5R)-N-4-tert-butoxycarbonyl-N-methylamino-5-hydroxyl-2(E)-hexenoate 8 and benzaldehyde in the presence of a base.Methyl (4S,5R)-4-azido-5-hydroxy-2(E)-hexenoateC7H11N3O3[α]D23=+52.9 (c 0.82, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4S,5R)Methyl (4R,5S)-5-acetoxy-4-azido-2(E)-hexenoateC9H13N3O4[α]D23=-44.1 (c 0.78, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S)Methyl β-d-vicenisaminideC8H17NO3[α]D22=-3.7 (c 0.4, MeOH)Ee = >99%Source of chirality: lipaseAbsolute configuration: (2R,3R,4S,6R)
Co-reporter:Yuki Iwaki, Masahiro Kaneko, Hiroyuki Akita
Tetrahedron: Asymmetry 2009 Volume 20(Issue 3) pp:298-304
Publication Date(Web):26 February 2009
DOI:10.1016/j.tetasy.2008.12.031
The first synthesis of (+)-myxothiazol A 1 was achieved based on a modified Julia olefination between (3,5R)-dimethoxy-(4R)-methyl-6-oxo-(2E)-hexenamide 3, corresponding to the left side of the final molecule, and 4-(2″-benzothiazolyl)sulfonylmethyl-2′-[(1′″R),6′″-dimethylhepta-(2′″E),(4′″E)-dienyl]-2,4′-bithiazole 6, corresponding to the right side. The synthesis of (+)-myxothiazol Z 2 was also achieved based on modified Julia olefination between (3,5R)-dimethoxy-(4R)-methyl-6-oxo-(2E)-hexenoate 4, corresponding to left side of the final molecule, and (S)-sulfone 6.n-Butyl 2-hydroxy-3-methyl-5-trimethylsilyl-4-pentynoateC13H24O3SiEe = >99%[α]D24=-7.6 (c 1.09, CHCl3)Source of chirality: lipaseAbsolute configuration: (2R,3S)n-Butyl 3-methyl-2-methoxy-5-trimethylsilyl-4-pentynoateC14H26O3SiEe = >99%[α]D24=+0.8 (c 1.54, CHCl3)Source of chirality: lipaseAbsolute configuration: (2R,3S)3-Methyl-2-methoxy-5-trimethylsilyl-4-pentyn-1-olC7H12O2Ee = >99%[α]D27=-27.6 (c 1.05, CHCl3)Source of chirality: lipaseAbsolute configuration: (2R,3S)tert-Butyldimethylsiloxy-3-methyl-2-methoxy-4-pentynC13H26O2SiEe = >99%[α]D25=-4.7 (c 1.06, CHCl3)Source of chirality: lipaseAbsolute configuration: (2R,3S)Methyl 6-tert-butyldimethylsiloxy-4-methyl-5-methoxy-2-hexynoateC15H28O4SiEe = >99%[α]D24=-15.1 (c 0.86, CHCl3)Source of chirality: lipaseAbsolute configuration: (4S,5R)Methyl 6-tert-butyldimethylsiloxy-3,5-dimethoxy-4-methyl-2(Z)-hexenoateC16H32O5SiEe = >99%[α]D24=-15.6 (c 0.96, CHCl3)Source of chirality: lipaseAbsolute configuration: (4R,5R)Methyl 6-tert-butyldimethylsiloxy-3,5-dimethoxy-4-methyl-2(E)-hexenamideC15H31NO4SiEe = >99%[α]D27=+35.7 (c 0.84, CHCl3)Source of chirality: lipaseAbsolute configuration: (4R,5R)Methyl 3,5-dimethoxy-4-methyl-6-oxo-(2E)-hexenoateC10H16O5Ee = >99%[α]D23=+104.7 (c 0.55, CHCl3)Source of chirality: lipaseAbsolute configuration: (4R,5R)4-Ethoxycarbonyl-2′-(1-benzothiazolylsulfanyl-methylethyl)-2,4′-bithiazoleC19H17N3O2S4Ee = >99%[α]D26=-92.9 (c 1.48, CHCl3)Source of chirality: lipaseAbsolute configuration: (S)4-Benzothiazolylsulfanylmethyl-2′-(1-benzo-thiazolylsulfonylmethylethyl)-2,4′-bithiazoleC24H18N4O2S6Ee = >99%[α]D26=-74.4 (c 0.77, CHCl3)Source of chirality: lipaseAbsolute configuration: (S)4-(2″-Benzothiazolyl)sulfanylmethyl-2′-[1″′,6″′-dimethylhepta-(2″′E),(4″′E)-dienyl]-2,4′-bithiazoleC23H23N3SEe = >99%[α]D27=+7.8 (c 0.525, CHCl3)Source of chirality: lipaseAbsolute configuration: (S)Myxothiazol AC25H33N3O3S2Ee = >99%[α]D26=+33.5 (c 0.70, MeOH)Source of chirality: lipaseAbsolute configuration: (4R,5S,1S)Myxothiazol ZC26H34N2O4S2Ee = >99%[α]D27=+85.7 (c 1.66, MeOH)Source of chirality: lipaseAbsolute configuration: (4R,5S,1S)
Co-reporter:Mikio Fujii, Sumie Yasuhara, Hiroyuki Akita
Tetrahedron: Asymmetry 2009 Volume 20(Issue 11) pp:1286-1294
Publication Date(Web):19 June 2009
DOI:10.1016/j.tetasy.2009.04.015
The lipase-catalyzed enantioselective acetylation of racemic methyl (4S∗,5S∗)-4-aryl-5-hydroxyhex-2(E)-enoates 1a–h was performed and efficient resolutions were achieved (E >400) by using CAL-B. After brosylation of the obtained optically active 1a–h, solvolysis of brosylates 13a–h afforded the corresponding methyl (4S∗,5S∗)-5-aryl-4-hydroxyhex-2(E)-enoates 3a–h (26–94% yield). The yields of 3a and 3c on the solvolysis of the corresponding 13 were 92% and 40%, respectively, while solvolysis of the corresponding tosylate was reported at 70% and 17%, respectively. This procedure is a facile and practical route to the synthesis of bioactive and optically active bisabolane-type sesquiterpenes.(4S,5S)-Methyl 5-hydroxy-4-(2,5-dimethoxyphenyl)hex-2(E)-enoateC15H20O5Ee = 95.2%ee[α]D29=+4.1 (c 1.10, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4S,5S)(4S,5S)-Methyl 5-hydroxy-4-(3,4-dimethoxyphenyl)hex-2(E)-enoateC15H20O5Ee = 98.6%ee[α]D27=+15.1 (c 1.26, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4S,5S)(4S,5S)-Methyl 5-hydroxy-4-(2,5-dimethoxy-4-methylphenyl)hex-2(E)-enoateC16H22O5Ee = 99.8%ee[α]D29=+10.5 (c 1.36, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4S,5S)(4S,5S)-Methyl 5-acetoxy-4-(4-methoxyphenyl)hex-2(E)-enoateC16H20O5Ee = 99.8%ee[α]D21=-5.5 (c 2.44, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R,5R)(4S,5S)-Methyl 5-acetoxy-4-(2-methoxy-4-methylphenyl)hex-2(E)-enoateC17H22O5Ee = 98.5%ee[α]D23=+1.8 (c 1.12, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R,5R)(4S,5S)-Methyl 5-hydroxy-4-(4-methoxyphenyl)hex-2(E)-enoateC14H18O4Ee = >99.9%ee[α]D23=+21.2 (c 2.07, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4S,5S)(4S,5S)-Methyl 5-hydroxy-4-(2-methoxy-4-methylphenyl)hex-2(E)-enoateC15H20O4Ee = >99%ee[α]D23=+2.0 (c 1.10, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4S,5S)(4S,5S)-Methyl 5-hydroxy-4-(4-methoxy-2-methylphenyl)hex-2(E)-enoateC15H20O4Ee = >99%ee[α]D29=-14.2 (c 1.00, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4S,5S)(4S,5S)-Methyl 5-hydroxy-4-(2-methoxy-5-methylphenyl)hex-2(E)-enoateC15H20O4Ee = 99.3%ee[α]D27=+17.6 (c 1.01, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4S,5S)(4S,5S)-Methyl 5-hydroxy-4-(3-methoxy-4-methylphenyl)hex-2(E)-enoateC15H20O4Ee = 98.2%ee[α]D27=-1.7 (c 1.01, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4S,5S)(4S,5S)-Methyl 5-acetoxy-4-(4-methoxy-2-methylphenyl)hex-2(E)-enoateC17H22O3Ee = 99.8%ee[α]D29=+18.6 (c 1.11, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R,5R)(4S,5S)-Methyl 5-acetoxy-4-(2-methoxy-5-methylphenyl)hex-2(E)-enoateC17H22O5Ee = 98.2%ee[α]D27=-10.0 (c 1.01, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R,5R)(4S,5S)-Methyl 5-acetoxy-4-(3-methoxy-4-methylphenyl)hex-2(E)-enoateC17H22O5Ee = 99.8%ee[α]D23=+12.5 (c 1.07, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R,5R)(4S,5S)-Methyl 5-acetoxy-4-(2,5-dimethoxyphenyl)hex-2(E)-enoateC17H22O6Ee = 98.2%ee[α]D25=+6.5 (c 1.03, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R,5R)(4S,5S)-Methyl 5-acetoxy-4-(3,4-dimethoxyphenyl)hex-2(E)-enoateC17H22O6Ee = 98.0%ee[α]D27=+11.2 (c 1.07, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R,5R)(4S,5S)-Methyl 5-acetoxy-4-(2,5-dimethoxy-4-methylphenyl)hex-2(E)-enoateC18H24O6Ee = 99.8%ee[α]D14=+5.6 (c 0.36, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (4R,5R)(4S,5S)-Methyl 4-hydroxy-5-(4-methoxyphenyl)hex-2(E)-enoateC14H18O4Ee = >99%ee[α]D23=-12.9 (c 1.01, CHCl3)Source of chirality: stereoselective rearrangementAbsolute configuration: (4S,5S)(4S,5S)-Methyl 4-hydroxy-5-(4-methoxy-2-methylphenyl)hex-2(E)-enoateC15H20O4Ee = >99%ee[α]D20=-11.7 (c 1.40, CHCl3)Source of chirality: stereoselective rearrangementAbsolute configuration: (4S,5S)(4S,5S)-Methyl 4-hydroxy-5-(2-methoxy-4-methylphenyl)hex-2(E)-enoateC15H20O4Ee = >99%ee[α]D20=+25.1 (c 0.53, CHCl3)Source of chirality: stereoselective rearrangementAbsolute configuration: (4S,5S)(4S,5S)-Methyl 4-hydroxy-5-(4-methoxy-3-methylphenyl)hex-2(E)-enoateC15H20O4Ee = 99.3%ee[α]D21=-8.4 (c 1.00, CHCl3)Source of chirality: stereoselective rearrangementAbsolute configuration: (4S,5S)(4S,5S)-Methyl 4-hydroxy-5-(2,5-dimethoxyphenyl)hex-2(E)-enoateC15H20O4Ee = 98.2%ee[α]D21=0 (c 0.78, CHCl3)Source of chirality: stereoselective rearrangementAbsolute configuration: (4S,5S)(4S,5S)-Methyl 4-hydroxy-5-(3,4-dimethoxyphenyl)hex-2(E)-enoateC15H20O5Ee = 95.2%ee[α]D21=-4.1 (c 0.60, CHCl3)Source of chirality: stereoselective rearrangementAbsolute configuration: (4S,5S)(4S,5S)-Methyl 4-hydroxy-5-(2,5-dimethoxyphenyl)hex-2(E)-enoateC15H20O5Ee = 98.6%ee[α]D23=-12.1 (c 1.21, CHCl3)Source of chirality: stereoselective rearrangementAbsolute configuration: (4S,5S)(4S,5S)-Methyl 4-hydroxy-5-(2,5-dimethoxy-4-methylphenyl)hex-2(E)-enoateC16H22O5Ee = 99.8%ee[α]D23=-5.8 (c 1.22, CHCl3)Source of chirality: stereoselective rearrangementAbsolute configuration: (4S,5S)
Co-reporter:Hideaki Akaike, Hidekazu Horie, Keisuke Kato, Hiroyuki Akita
Tetrahedron: Asymmetry 2008 Volume 19(Issue 9) pp:1100-1105
Publication Date(Web):16 May 2008
DOI:10.1016/j.tetasy.2008.04.011
Syntheses of (+)-asperlin 1 were achieved via two different synthetic routes. 1,2-Addition of α-furyl anion to (2R,3S)-2-tbutyldimethylsilyloxy-3-chlorobutanal 6 gave (1S,2R,3S)-1-(2-furyl)-2-tbutyldimethylsilyloxy-3-chlorobutanol 7, which was converted to the chiral intermediate, (1S,2R,3R)-1-(2-furyl)-2,3-epoxybutanol 8 (37% overall yield from 6) for the synthesis of (+)-1. The second synthesis of (+)-asperlin 1 from (2R,3S)-6 was achieved in 8% overall yield, based on a combination of the indium-assisted stereoselective addition of 3-bromopropenyl acetate 9 to (2R,3S)-6 and the ring closing metathesis (RCM) using Grubbs catalyst.(1S,2R,3R)-1-(2-Furyl)-2,3-epoxybutanolC8H10O3Ee = >99%[α]D24=-42.2 (c 0.67, CHCl3)Source of chirality: lipaseAbsolute configuration: (1S,2R,3R)(3R,4R,5S,6R)-3-Acetoxy-4-acryloyloxy-5,6-epoxy-1-hepteneC12H16O5Ee = >99%[α]D25=+19.1 (c 0.54, EtOH)Source of chirality: lipaseAbsolute configuration: (3R,4R,5S,6R)
Co-reporter:Yuki Iwaki, Shigeo Yamamura, Hiroyuki Akita
Tetrahedron: Asymmetry 2008 Volume 19(Issue 18) pp:2192-2200
Publication Date(Web):22 September 2008
DOI:10.1016/j.tetasy.2008.08.029
Convergent syntheses of (14R,15)- and (14S,15)-dihydroxycystothiazole A 4 were achieved based on a Julia-Kocienski coupling between the functionalized aldehyde (2E)-6 or (2Z)-6, corresponding to the left-side, and chiral sulfones (14R)-16 and (14S)-16, bearing a bithiazole moiety corresponding to the right-side, respectively. The absolute configuration of natural (14,15)-dihydroxycystothiazoles A 4 was determined to be (4R,5S,14S) by comparison of the physical data, including the sign of specific rotation, between synthetic (2E,4R,5S,6E,14S)-4 and natural 4. Deprotections of the silyl group and cyclopentane moiety of the coupled product (2E,4R,5S,6E,14R)-17 gave (14R,15)-dihydroxycystothiazole C 5, which was consistent with natural 5 corresponding to the minor isomer, including the sign of specific rotation. Likewise, deprotection of the silyl group and cyclopentane moiety of the coupled product (2E,4R,5S,6E,14S)-17 afforded (14S,15)-dihydroxycystothiazole C 5, which was consistent with natural 5 corresponding to the major isomer, including the sign of specific rotation. Finally, convergent synthesis of 14-hydroxycystothiazole C 3 was achieved based on the modified (one-pot) Julia olefination between the aldehyde (2Z)-6 and bithiazole sulfone 22. The absolute configurations of natural 14-hydroxycystothiazole C 3 were confirmed to be (4R) and (5S). Methylation of synthetic 3 gave cystothiazole B 2.14-Hydroxycystothiazole CC19H24N2O5S2[α]D22=+112.6 (c 1.17, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S)(14R,15)-Dihydroxycystothiazole AC20H26N2O6S2[α]D23=+113.0 (c 0.76, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S,14R)(14S,15)-Dihydroxycystothiazole AC20H26N2O6S2[α]D24=+77.8 (c 0.675, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S,14S)(14R,15)-Dihydroxycystothiazole CC19H24N2O6S2[α]D24=+145.9 (c 0.64, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S,14R)(14S,15)-Dihydroxycystothiazole CC19H24N2O6S2[α]D25=+91.1 (c 1.00, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S,14S)
Co-reporter:Noriyuki Sutou, Keisuke Kato, Hiroyuki Akita
Tetrahedron: Asymmetry 2008 Volume 19(Issue 15) pp:1833-1838
Publication Date(Web):8 August 2008
DOI:10.1016/j.tetasy.2008.07.013
Concise syntheses of (−)-indolmycin 1 and (−)-5-methoxyindolmycin 3 were developed based on a palladium-catalyzed reaction of (2S,3R)-2-acetoxy-3-methyl-5-trimethylsilyl-4-pentynoate 6 with an o-iodoaniline derivative 10 or 11, followed by reaction with guanidine hydrochloride in the presence of base. An optically active internal alkyne (2S 3R)-6 was obtained by lipase-assisted enantioselective acetylation of (±)-(2,3)-syn-2-hydroxy-3-methyl-5-trimethylsily-4-pentynoate 4.(2R,3S)-2-Hydroxy-3-methyl-5-trimethylsilyl-4-pentynoateC10H18O3SiEe = 94%[α]D25=-24.8 (c 1.13, CHCl3)Source of chirality: lipaseAbsolute configuration: (2R,3S)(2S,3R)-2-Acetoxy-3-methyl-5-trimethylsilyl-4-pentynoateC12H20O4SiEe = 95%[α]D27=+12.05 (c 1.09, CHCl3)Source of chirality: lipaseAbsolute configuration: (2S,3R)
Co-reporter:Yuusuke Arima, Masako Kinoshita, Hiroyuki Akita
Tetrahedron: Asymmetry 2007 Volume 18(Issue 14) pp:1701-1711
Publication Date(Web):30 July 2007
DOI:10.1016/j.tetasy.2007.07.010
Both enantiomers (8aR)-7 and (8aS)-7 of bicyclofarnesol were synthesized from the enzymatic resolution products (1R,4aR,8aR)-1,2,3,4,4a,5,6,7,8,8a-decahydro-5,5,8a-trimethyl-2-oxo-trans-naphthalene-1-methanol-2-ethylene acetal (8aR)-5 (98% ee) and acetate of (1S,4aS,8aS)-1,2,3,4,4a,5,6,7,8,8a-decahydro-5,5,8a-trimethyl-2-oxo-trans-naphthalene-1-methanol-2-ethylene acetal (8aS)-6 (>99% ee), respectively. The formal synthesis of (+)-wiedendiol 1 was achieved via a coupling reaction of an ate complex derived from 1,2,4-trimethoxybenzene with allyl bromide (8aS)-8 derived from (8aS)-7. The total synthesis of (+)-norsesterterpene diene ester 2 was achieved, based on the synthesis of (13E,10S)-α,β-unsaturated aldehyde 12, derived from (8aS)-7, followed by the selective construction of the (3E,5E)-diene moiety including a C(2)-stereogenic centre in (+)-2. The total synthesis of (−)-subersic acid 3 was carried out based on a Stille coupling between allyl trifluoroacetate congener 25c, derived from (8aR)-7, corresponding to the diterpene part, and aryl stannane congener 26 in the presence of Pd catalyst and CuI as an additive.(+)-1,2,4-Trimethoxy-3-[5′S,10′S,8′(9′)-drimen-11′-yl]benzeneC24H36O3Ee = >99%[α]D22=+69.7 (c 1.71, CHCl3)Source of chirality: lipaseAbsolute configuration: (5′S,10′S)(+)-Norsesterterpene diene esterC25H40O2Ee = >99%[α]D24=+12.4 (c 0.55, CHCl3)Source of chirality: lipaseAbsolute configuration: (2R,13S,18S)(−)-Subersic acidC27H38O3Ee = 98%[α]D24=-46.7 (c 0.17, CHCl3)Source of chirality: lipaseAbsolute configuration: (5R,10R)
Co-reporter:Hiroyuki Akita, Yuki Iwaki, Keisuke Kato, Jianhua Qi, Makoto Ojika
Tetrahedron: Asymmetry 2007 Volume 18(Issue 4) pp:513-519
Publication Date(Web):12 March 2007
DOI:10.1016/j.tetasy.2007.02.011
Total synthesis of (4R,5S,6E,14S)- and (4R,5S,6E,14R)-cystothiazoles F 3 was achieved from the chiral bithiazole-type primary alcohols [(S)- and (R)-4-ethoxycarbonyl-2′-(1-hydroxymethylethyl)-2,4′-bithiazoles 8], which were obtained based on the enzymatic resolution of racemic alcohol 8 and its acetate 9. From a direct comparison by means of chiral HPLC between natural cystothiazole F 3 and synthetic compounds [(4R,5S,6E,14S)- and (4R,5S,6E,14R)-cystothiazoles 3], natural cystothiazole F 3 was found to be a 33:67 diastereomeric mixture [(4R,5S,6E,14S)-3:(4R,5S,6E,14R)-3 = 33:67].(4R,5S,6E,14S)-Cystothiazole FC20H27N2O5S2[α]D26=+86.2 (c 1.05, CHCl3)Ee = 99%Source of chirality: lipaseAbsolute configuration: (4R,5S,6E,14S)(4R,5S,6E,14R)-Cystothiazole FC20H27N2O5S2[α]D26=+94.6 (c 0.78, CHCl3)Ee = 99%Source of chirality: lipaseAbsolute configuration: (4R,5S,6E,14R)
Co-reporter:Takahiro Miyake, Hideo Kigoshi, Hiroyuki Akita
Tetrahedron: Asymmetry 2007 Volume 18(Issue 24) pp:2915-2922
Publication Date(Web):10 December 2007
DOI:10.1016/j.tetasy.2007.11.024
The enzymatic resolution products [(1R,4aR,8aR)-1,2,3,4,4a,5,6,7,8,8a-decahydro-5,5,8a-trimethyl-2-oxo-trans-naphthalene-1-methanol-2-ethylene acetal (8aR)-7 (98% ee) and {acetate of (1S,4aS,8aS)-1,2,3,4,4a,5,6,7,8,8a-decahydro-5,5,8a-trimethyl-2-oxo-trans-naphthalene-1-methanol-2-ethylene acetal} (8aS)-9 (>99% ee)] obtained by the lipase-catalyzed enantioselective acetylation of (±)-7 in the presence of vinyl acetate as an acyl donor were converted to the α,β-unsaturated ketones (8aR)-6 and (8aS)-6, respectively. Concise syntheses of (+)-totarol 1, (+)-podototarin 2 and (+)-sempervirol 3 were achieved based on Michael reactions between (8aS)-6 and the appropriate β-keto ester followed by aldol condensation. The first chiral syntheses of (+)-jolkinolides E 4 and D 5 were achieved from (5R,10R,12R)-12-hydroxypodocarpa-8(14)-en-13-one 15 derived from (8aR)-6.(+)-TotarolC20H30O[α]D27=+41.9 (c 1.0, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (5S,10S)(+)-SempervirolC20H30O[α]D23=+54.2 (c 1.0, CHCI3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (5S,10S)(+)-Jolkinolide EC20H28O2[α]D21=+337 (c 0.6, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (5R,9S,10R,12R)(+)-Jolkinolide DC20H28O3[α]D21=+301 (c 0.5, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (5R,9S,10R,12R,13S)
Co-reporter:Hiroyuki Akita, Yoshiki Takano, Katsushi Nedu, Keisuke Kato
Tetrahedron: Asymmetry 2006 Volume 17(Issue 11) pp:1705-1714
Publication Date(Web):17 July 2006
DOI:10.1016/j.tetasy.2006.06.010
A stereoselective synthesis of a versatile chiral synthon possessing two stereogenic centers, (2S,3S)-3-[2-(5-benzyloxypyridyl)]-2-methyl-1,3-propane diol 12 (>99% ee), was achieved by using a chemo-enzymatic method. The conversion of (2S,3S)-12 to the homochiral intermediate (2S,3S,4S)-2-benzyloxycarbonylamino-4-[2-(5-benzyloxypyridyl)]-4-tert-butyldimethylsilyloxy-3-methylbutanoic acid 2 corresponding to the N-terminal amino acid congener of nikkomycin Z 1 is described.(2S,3S)-3-[2-(5-Benzyloxypyridyl)]-2-methyl-1,3-propane diolC16H19NO3[α]D26=-28.6 (c 0.92, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (2S,3S)(2R,3R)-1-Acetoxy-3-[2-(5-benzyloxypyridyl)]-2-methyl-3-propanolC18H21NO4[α]D29=+19.6 (c 0.98, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (2R,3R)
Co-reporter:Naoko Fujiwara, Masako Kinoshita, Hiroyuki Akita
Tetrahedron: Asymmetry 2006 Volume 17(Issue 21) pp:3037-3045
Publication Date(Web):17 November 2006
DOI:10.1016/j.tetasy.2006.11.015
The convergent synthesis of (+)-ambrein 1 was achieved based on a modified Julia coupling reaction between aldehyde 14 corresponding to the left-half A and sulfone 25a or 25b corresponding to the right-half B. Aldehyde 14 was synthesized in 14% overall yield (nine steps) from the enzymatic resolution product, epoxy alcohol (8aS)-2. Sulfone 25a or 25b was synthesized in 11 steps (25a: 41% overall yield, 25b: 56% overall yield) from the enzymatic resolution product, (1S,6S)-2,2-dimethyl-6-hydroxyhexane-1-carboxylate 4.(+)-AmbreinC30H52OEe = >99%[α]D24=+18.9 (c 0.47, EtOH)Source of chirality: lipaseAbsolute configuration: (1R,2R,4aS,8aS,1″S)
Co-reporter:Msashi Kishida, Hiroyuki Akita
Tetrahedron: Asymmetry 2005 Volume 16(Issue 15) pp:2625-2630
Publication Date(Web):1 August 2005
DOI:10.1016/j.tetasy.2005.06.040
The Rosavin framework could be constructed with either phenylboronic acids, the protected arabinopyranosyl bromide 4 or the protected xylopyranosyl bromide 5, along with allyl O-β-d-glucopyranoside 7 that could be easily prepared based on direct β-glucosidation between allyl alcohol and d-glucose using the immobilized β-glucosidase (EC 3.2.1.21). The key reaction was the Pd(II)-catalyzed Mizoroki-Heck type reaction between allyl β-d-glucopyranoside congeners 9 or 10 and arylboronic acids. Deprotection of the coupling products afforded synthetic Rosavin 1, 4-methoxycinnamyl 6-O-(α-l-arabinopyranosyl)-β-d-glucopyranoside 2, and cinnamyl 6-O-(β-d-xylopyranosyl)-β-d-glucopyranoside 3, which were identical with the natural products in respect to the specific rotation and spectral data.The synthesis of Rosavin 1 was achieved by the coupling reaction of allyl β-d-glucopyranoside congener 2 and bromide 3 followed by the Pd(II)-catalyzed MH-type reaction with phenylboronic acid. Moreover, Rosavin analogues were obtained using same synthetic strategy.Allyl 6-O-tert-butyldimethylsilyl-β-d-glucopyranosideC15H30O6Si[α]D27=-45.9 (c 0.75, CHCl3)Ee = >99%Source of chirality: d-glucoseAllyl 2,3,4-tri-O-benzoyl-β-d-glucopyranosideC30H28O9[α]D27=-0.7 (c 0.54, CHCl3)Ee = >99%Source of chirality: d-glucoseAllyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-α-l-arabinopyranosyl)-β-d-glucopyranosideC56H48O16[α]D27=-72.9 (c 0.62, CHCl3)Ee = >99%Source of chirality: d-glucoseAllyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-β-d-xylopyranosyl)-β-d-glucopyranosideC56H48O16[α]D27=-24.9 (c 0.51, CHCl3)Ee = >99%Source of chirality: d-glucoseCinnamyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-α-l-arabinopyranosyl)-β-d-glucopyranosideC62H52O16[α]D27=+51.8 (c 0.50, CHCl3)Ee = >99%Source of chirality: d-glucose4-Methoxycinnamyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-α-l-arabinopyranosyl)-β-d-glucopyranosideC63H54O17[α]D27=+54.6 (c 0.28, CHCl3)Ee = >99%Source of chirality: d-glucoseCinnamyl2,3,4-tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-β-d-xylopyranosyl)-β-d-glucopyranosideC62H52O16[α]D27=-35.3 (c 0.53, CHCl3)Ee = >99%Source of chirality: d-glucoseRosavin (Cinnamyl 6-O-(α-l-arabinopyranosyl)-β-d-glucopyranoside)C20H28O10[α]D27=-54.7 (c 0.70, CHCl3/MeOH 1:1)Ee = >99%Source of chirality: d-glucose4-Methoxycinnamyl 6-O-(α-l-arabinopyranosyl)-β-d-glucopyranosideC21H30O11[α]D25=-46.6 (c 0.31, MeOH)Ee = >99%Source of chirality: d-glucoseCinnamyl 6-O-(β-d-xylopyranosyl)-β-d-glucopyranosideC20H28O10[α]D24=-71.9 (c 0.40, MeOH)Ee = >99%Source of chirality: d-glucose
Co-reporter:Hiroyuki Akita, Eiji Kawahara, Keisuke Kato
Tetrahedron: Asymmetry 2004 Volume 15(Issue 20) pp:3329
Publication Date(Web):18 October 2004
DOI:10.1016/j.tetasy.2004.09.001
Co-reporter:Hiroyuki Akita;Hiroshi Nakamura;Machiko Ono
Chirality 2003 Volume 15(Issue 4) pp:352-359
Publication Date(Web):19 MAR 2003
DOI:10.1002/chir.10203
The total synthesis of (+)-macrosphelide A (1) (18.5% overall yield in 11 steps), (+)-macrosphelide C (2) (25% overall yield in 9 steps), (+)-macrosphelide E (3) (23.9% overall yield in 11 steps), (+)-macrosphelide F (4) (20% overall yield in 9 steps), and (+)-macrosphelide G (5) (22% overall yield in 9 steps) was achieved from a chemoenzymatic reaction product (4R,5S)-4-benzyloxy-5-hydroxy-2(E)-hexenoate 10. Chirality 15:352–359, 2003. © 2003 Wiley-Liss, Inc.
Co-reporter:Hiroshi Nakamura, Machiko Ono, Yuki Shida, Hiroyuki Akita
Tetrahedron: Asymmetry 2002 Volume 13(Issue 7) pp:705-713
Publication Date(Web):2 May 2002
DOI:10.1016/S0957-4166(02)00180-5
The total synthesis of (+)-macrosphelide C 1 (25% overall yield in nine steps), (+)-macrosphelide F 2 (20% overall yield in nine steps) and (+)-macrosphelide G 3 (22% overall yield in nine steps) has been achieved from the chemoenzymatic reaction product (4R,5S)-4-benzyloxy-5-hydroxy-(2E)-hexenoate 7.Total synthesis of (+)-macrosphelides C 1 (25% overall yield in nine steps), F 2 (20% overall yield in nine steps) and G 3 (22% overall yield in nine steps) were achieved from the chemoenzymatic reaction product (4R,5S)-4-benzyloxy-5-hydroxy-(2E)-hexenoate 4.Benzyl macrosphelide CC23H28O7E.e. >99%[α]D19=−43.7 (c=0.22, CHCl3)Source of chirality: lipase-catalysed enantioselective hydrolysisAbsolute configuration: 3S,9S,14R,15SMacrosphelide CC16H22O7E.e. >99%[α]D26=+53.3 (c=0.08, EtOH)Source of chirality: lipase-catalysed enantioselective hydrolysisAbsolute configuration: 3S,9S,14R,15SBenzyl macrosphelide FC23H28O7E.e. >99%[α]D24=−19.7 (c=0.16, CHCl3)Source of chirality: lipase-catalysed enantioselective hydrolysisAbsolute configuration: 3R,9S,14R,15SMacrosphelide FC16H22O7E.e. >99%[α]D27=+42.8 (c=0.50, EtOH)Source of chirality: lipase-catalysed enantioselective hydrolysisAbsolute configuration: 3R,9S,14R,15SBenzyl macrosphelide GC23H28O7E.e. >99%[α]D29=−22.1 (c=0.35, CHCl3)Source of chirality: lipase-catalysed enantioselective hydrolysisAbsolute configuration: 3R,8R,9S,15SMacrosphelide GC16H22O7E.e. >99%[α]D26=+51.7 (c=0.35, EtOH)Source of chirality: lipase-catalysed enantioselective hydrolysisAbsolute configuration: 3R,8R,9S,15S
Co-reporter:Chikako Saotome, Machiko Ono, Hiroyuki Akita
Tetrahedron: Asymmetry 2000 Volume 11(Issue 20) pp:4137-4151
Publication Date(Web):20 October 2000
DOI:10.1016/S0957-4166(00)00395-5
A conjugated addition of benzylamine to methyl (4R,5S)-4,5-(isopropylidenedioxy)-(2E)-hexenoate 8a followed by lactonization under acidic condition proceeds to the formal total syntheses of l-daunosamine 4 and l-acosamine 2. On the other hand, direct conjugated addition of benzylamine to methyl (4S,5S)-4,5-epoxy-(2E)-hexenoate 5 and the subsequent intramolecular nucleophilic attack by the ester carbonyl group on the epoxy ring of the substrates leads to the formal total syntheses of d-acosamine 2 and d-ristosamine 1.
Co-reporter:Keisuke Kato, Machiko Ono, Hiroyuki Akita
Tetrahedron: Asymmetry 1997 Volume 8(Issue 14) pp:2295-2298
Publication Date(Web):24 July 1997
DOI:10.1016/S0957-4166(97)00253-X
Stereoselective total syntheses of (−)-(4S,5R)- and (+)-(4R,5S)-chuangxinmycins1 were achieved based on the enzymatic syntheses of (2R,3S)- and (2S,3R)-epoxy butanoates 8, respectively. Chiral intermediates such as (2R,3S)- and (2S,3R)-2-hydroxy-3-(4′-iodoindol-3′-yl)butanoate 5 for the chiral synthesis of (−)- and (+)-1 were also obtained by the enantioselective hydrolysis of the corresponding acetate 6 by lipase.Stereoselective total syntheses of (−)-(4S,5R)- and (+)-(4R,5S)-chuangxinmycins 1 were achieved based on the enzymatic syntheses of (2R,3S)-(2S,3R)-epoxy butanoate 2, respectively.
Co-reporter:Mikio Fujii, Sadayuki Ishii, Ryota Saito, Hiroyuki Akita
Journal of Molecular Catalysis B: Enzymatic (August 2009) Volume 59(Issue 4) pp:254-260
Publication Date(Web):1 August 2009
DOI:10.1016/j.molcatb.2008.07.004
The optical resolution of racemic albicanol (rac-1) based on the lipase-catalyzed transesterification by using vinyl myristate as an acyl donor afforded (8aR)-1 (99% ee) in 43% yield and (8aS)-1 (99% ee) in 37%. E value of the enzymatic reaction was 56.7 which was superior to that of the reported value (E = 25) by using isopropenyl acetate as an acyl donor. As the synthetic application of obtained (8aR)-1, (−)-copalic acid ((8aR)-3) and (−)-copalol ((8aR)-4) were synthesized from (8aR)-1 in 35% and 34% total yield, respectively.
Co-reporter:Noriyuki Sutou, Keisuke Kato, Hiroyuki Akita
Tetrahedron: Asymmetry (8 August 2008) Volume 19(Issue 15) pp:1833-1838
Publication Date(Web):8 August 2008
DOI:10.1016/j.tetasy.2008.07.013
Concise syntheses of (−)-indolmycin 1 and (−)-5-methoxyindolmycin 3 were developed based on a palladium-catalyzed reaction of (2S,3R)-2-acetoxy-3-methyl-5-trimethylsilyl-4-pentynoate 6 with an o-iodoaniline derivative 10 or 11, followed by reaction with guanidine hydrochloride in the presence of base. An optically active internal alkyne (2S 3R)-6 was obtained by lipase-assisted enantioselective acetylation of (±)-(2,3)-syn-2-hydroxy-3-methyl-5-trimethylsily-4-pentynoate 4.Download full-size image