SYNTHETIC STUDIES OF STEROID DERIVATIVES CONTAINING 9-MEMBERED LACTONE

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10650858
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: TSURUOKA NATIONAL COLLEGE OF TECHNOLOGY
• Principal Investigator: KIDO FUSAO TSURUOKA NATIONAL COLLEGE OF TECHNOLOGY, TSURUOKA NATIONAL COLLEGE OF TECHNOLOGY MATERIAL SCIENCE & ENGINEERING, PROFESSOR (20006315)
• Project Period (FY): 1998 – 1999
• Keywords: Glaucogenin A / Pai-ch'en / Furof[2.3-b]furan / mannitol / 9-membered lactone / Diels-Alder Reaction

Research Abstract

Glaucogenin A , one of the constituent of Chinese medicine Pai-ch'ien, is a 13,14:14,15-disecopregnanesteroid having furo[2.3-b]furan ring and 9-membered lactone ring. Recently we have developed the chemistry of cyclic allyl sulfonium ylides and found a highly efficient synthetic method of functionalized (β-vinyl -γ- and δ lactones by the [2.3]sigmatropic rearrangement of cyclic allylsulfonium ylides generated from diazosulfides. To illustrate the efficiency of this reaction in organic synthesis we studied the sythesis of furo[2.3-b]furan ring, which is a part of glaucogenin A. Rearranged products, δ-substituted-β-vinyl-δ-lactones were submitted to ozonization and the resulting ozonides were reduced with dimethylsulfide to give corresponding aldehyde. when these aldehyde were treated with mineral acid, furofuranones were obtained in good yields. The other hand, treatment of aldehyde, readily prepared from 1,2:5,6-di-O-isopropyriden-D-mannitol by oxidation, with Triethyl phosphonoacetat e afforded α, β-unsatulated ester in high yield. Reduction of unsaturated ester with diisobutyl aluminum hydride, followed by Claisen rearrangement with triethylorthoacetate and hydroquinone afforded β-vinyl ester in high yield. Treatment of resulting ester with HCl-80% methanol afforded β-vinyl-γ-hydroxymethyl-γ-lactone in moderate yield.
The preparation of A, B ring of glaucogenin A started from 4-carbethoxy-3-methyl-2-cyclohexen-1-one (Hageman's ester). Treatment of Hageman's ester with ethylene glycol in the presence of p-toluenesulfonic acid in refluxing benzene afforded the ketal ester, in which the double bond was isomelized to 3,4-position.Reduction of ethyl ester with LiAIH_4 in THF, followd by oxidation with active MnO_2 in CH_2Cl_2 gave aldehyde.Resulting aldehyde was treated with Ph3P=CH2 in benzene afforded 4-Vinyl-3-methyl-3-cyclohexen-1-one acetal. The many attempts of Diels-Alder reaction between this olefin and some dienophile (diethyl acetylene dicarboxylate, maleic anhydride) could not obtain good results.