Limonoids are characterized by a polycyclic structure and show a wide variety of bioactivities. In particular, mesendanin L, 12-hydroxyamoorastatone, and meliatoosenin F have unique structures containing a trans-A/B/C and cis-C/D-fused tetracyclic skeleton. We synthesized the core structure of these limonoids via Mn(OAc)3 and Cu(OAc)2-mediated radical domino cyclization of an acyclic tetraene precursor having a terminal β-keto ester. To the best of our knowledge, this is the first example of the radical-mediated construction of a 6/6/6/5-membered tetracyclic skeleton.Download high-res image (148KB)Download full-size image

A stereoselective synthesis of scyphostatin hydrophilic moiety was accomplished. Substrate- and reagent-controlled dihydroxylation of tri- and monosubstituted alkenes afforded desired diols, respectively. Chemo- and stereoselective allylation of α-(methoxycarbonyl)cyclohexanone provided allylcyclohexanol. Oxidative cleavage of glycol and subsequent β-elimination of siloxycyclohexanone furnished the desired epoxycyclohexenone.

Steroid family has various bioactivities and characteristic polycyclic structure. Although several synthetic methods have been reported, more efficient way is desired for medicinal chemistry. In this Letter, we synthesized pseudoenantiomers of tricyclic enones toward both enantiomers for ABC-ring moiety of steroids utilizing d-mannitol as a chiral source. The key steps are radical domino cyclization of polyalkenyl-β-keto ester into tricyclic keto ester and subsequent dealkoxycarbonylation.Graphical abstract

Steroids with A/B cis-decalin moiety and various bioactivities have attracted many synthetic chemists as target molecules and development of efficient methodology providing cis-decalins has been desired. A stereoselective domino cyclization via Mn(OAc)3 and Cu(OTf)2-mediated radical reaction was found to be effective to construct cis-decalin framework.

The substrate specificity of an engineered Bacillus subtilis epoxide hydrolase, which so far had shown high activity and enantioselectivity with 1-benzyloxymethyl-1-methyloxirane, has been studied by altering the methyl substituent into hydrogen, oxygen-containing functionalities, and unsaturated homologs. High enantioselectivity (E = 44) was observed with 1-benzyloxymethyl-1-vinyloxirane with a proper catalytic activity. The elaboration of the reaction conditions and work-up procedures enabled a preparative-scale kinetic resolution, to give (R)-2-benzyloxymethyl-3-butene-1,2-diol and its antipodal (R)-epoxide in high ees.(R)-1-Benzyloxymethyl-1-vinyloxiraneC12H14O2Ee = 82.9%[α]D24=+28.9 (c 1.12, MeOH)Source of chirality: Bacillus subtilis epoxide hydrolase-catalysed hydrolysisAbsolute configuration: (R)(R)-2-Benzyloxymethyl-3-butene-1,2-diolC12H16O3Ee = 97.7%[α]D24=-28.1 (c 0.65, CH2Cl2)Source of chirality: Bacillus subtilis epoxide hydrolase-catalysed hydrolysisAbsolute configuration: (R)