36 シクリトール類を出発原料として用いた天然物合成(ポスター発表の部)

抄録

myo-Inositol (1) and L-quebrachitol (2) are representative cyclitols found abundantly in nature. In this paper, syntheses of some natural products in optically active forms utilizing 1 and 2 as the starting materials are described. 1. Total Synthesis of (+)- and (-)-Nojirimycin (17a and 17b) from myo-Inositol (1): The racemic diol (4), readily obtained from 1 in 3 steps, was converted into its L-O-acetyl mandelate derivatives (5a and 5b) and resolved. The cyclohexane ring of 5a was cleaved oxidatively in a regioselective manner by way of Baeyer-Villiger oxidation of ketone (7a), followed by acid treatment to give 9a. Introduction of the amino function into 12a with Mitsunobu reaction and deprotection gave 15a, which was converted into 16a. Treatment of 16a with basic resin afforded 17a. From 5b, compound 16b and 17b were also synthesized. Compound 16b was found to possess high inhibitory activity against β-glucosidase. 2. Formal Total Syntheses of (-)-Isoavenaciolide (31) and (-)-Ethisolide (37) from L-quebrachitol (2): The structurally interesting antifungal mold metabolite, (-)-isoavenaciolide and its homolog, (-)-ethisolide were synthesized from 2. Wittig olefination of the ketone (23), obtained from 2 in 9 steps, gave 24. Stereoselective hydrogenation of 24, followed by treatment with BBr_3 afforded the lactone 26. Periodate oxidation of 26 gave 27, which was converted into the known intermediate (30) for a synthesis of 31. Compound 27 was also converted into 36, which is a known synthetic precursor for 37. 3. Total Synthesis of Bengamide E (51) from L-Quebrachitol (2): Bengamide E (51) is a novel sponge-derived natural product and possesses a unique structure. The polyhydroxyl carboxylic acid moiety (48) of bengamide E was prepared stereoselectively from 2. Wittig reaction of L-mannofuranose derivative (41), obtained 4 steps from 2, gave 42. Inversion of the stereochemistry of the allyl alcohol and oxidation of the primary alcohol provided 49, which was condensed with cyclo-L-lysine to give 50. Deprotection afforded 51. This first synthesis of 51 fully confirmed the absolute configuration of this novel natural product.