Lycopene-5,6-diol stereoisomers (1a,b) and (2a,b) and γ-carotene-5′,6′-diol stereoisomers (3a,b) and (4a,b) were synthesized by a stepwise C15 + C10 + C15 double Wittig reaction strategy. The key compounds erythro(anti)-C15-dihydroxy aldehydes 17a,b and their threo(syn)-stereoisomers 23a,b were prepared via Sharpless asymmetric epoxidation of geraniol and nerol followed by acidic hydrolysis of the epoxides in a stereospecific manner. The enantiomerically enriched anti-isomers were obtained by way of recrystallization of 2,3-epoxygeranyl 3,5-dinitrobenzoates 9a,b, whereas syn-isomers were obtained as enantiomerically pure forms via recrystallization of dihydroxyneryl 3,5-dinitrobenzoates 21a,b. In order to determine the absolute stereochemistry of natural products, HPLC separation methods for each enantiomers 1a,b–4a,b were established by using a column carrying a chiral stationary phase.Download high-res image (128KB)Download full-size image

The first total syntheses of amarouciaxanthin A and B (C40) via the stereoselective Wittig reaction of C15-allenic and C15-acetylenic tri-n-butylphosphonium salts with the unprecedented C25-3,8-dihydroxy-5,6-epoxyapocarotenal have been completed. Oxidation of the two hydroxyl groups in the left part of the resulting condensation products followed by regioselective oxirane ring opening gave the target carotenoids.

Stereoselective total synthesis of the C40-diacetylenic carotenoid alloxanthin (1) and the C31-acetylenic apocarotenoid triophaxanthin (2) was accomplished by Wittig condensation of C10-dialdehyde 20 or C16-keto aldehyde 19, respectively, with C15-acetylenic tri-n-butylphosphonium salt 12.

N-Acylethanolamines (NAEs) including N-arachidonoylethanolamine (anandamide) and N-palmitoylethanolamine are endogenous lipid mediators. These molecules are degraded to the corresponding fatty acids and ethanolamine by fatty acid amide hydrolase (FAAH) or NAE-hydrolyzing acid amidase (NAAA). Lipophilic amines, especially pentadecylamine (2c) and tridecyl 2-aminoacetate (11b), were found to exhibit potent NAAA inhibitory activities (IC50 = 5.7 and 11.8 μM), with much weaker effects on FAAH. These simple structures would provide a scaffold for further improvement in NAAA inhibitory activity.

The synthesis of 3,6-epoxy carotenoids cucurbitaxanthin A 1, cycloviolaxanthin 2 and capsanthin 3,6-epoxide 3, was accomplished via the C15-3,6-epoxides 20e and 20f, prepared by the regioselective ring opening of the 3-hydroxy-5,6-epoxides 10e and 10f.

The synthesis of capsanthin 1 and capsorubin 2 was accomplished via the C15-cyclopentyl ketone 6 prepared by Lewis acid-promoted regio- and stereoselective rearrangement of the epoxy dienal 5.

Retinoidal γ-hydroxybutenolides 2a–d having various lengths of conjugated double bond were prepared in three steps from the corresponding aldehyde 4. Their biological activities were then measured. Of these compounds, only compound 2c possessing a structure similar to that of retinoic acid showed differentiation-inducing activity and very strong apoptosis-inducing activity in HL-60 cells.Retinoidal γ-hydroxybutenolides having various lengths of conjugated double bond were prepared, and their apoptosis-inducing and differentiation-inducing activities were tested in HL-60 cells.

The synthesis of 3,6-epoxy carotenoids cucurbitaxanthin A 1, cycloviolaxanthin 2 and capsanthin 3,6-epoxide 3, was accomplished via the C15-3,6-epoxides 20e and 20f, prepared by the regioselective ring opening of the 3-hydroxy-5,6-epoxides 10e and 10f.

The synthesis of capsanthin 1 and capsorubin 2 was accomplished via the C15-cyclopentyl ketone 6 prepared by Lewis acid-promoted regio- and stereoselective rearrangement of the epoxy dienal 5.

Stereoselective total synthesis of the C40-diacetylenic carotenoid alloxanthin (1) and the C31-acetylenic apocarotenoid triophaxanthin (2) was accomplished by Wittig condensation of C10-dialdehyde 20 or C16-keto aldehyde 19, respectively, with C15-acetylenic tri-n-butylphosphonium salt 12.