SYNTHETIC STUDIES OF STEROID DERIVATIVES CONTAINING 9-MEMBERED LACTONE

白倩素A是中药白倩的有效成分之一，是一种13，14：14，15-二甾体孕甾烷类化合物，含有呋喃并[2.3-B]呋喃环和9元内酯环。最近，我们发展了环状烯丙基锍叶立德的化学，发现了一种通过重氮硫化物生成的环状烯丙基锍叶立德的[2.3] σ转移重排来高效合成功能化β-乙烯基-γ-和δ-内酯的方法。为了说明该反应在有机合成中的有效性，我们研究了蓝绿皂苷元A的一部分呋喃并[2.3-B]呋喃环的合成。重排产物δ-取代-β-乙烯基-δ-内酯经臭氧化后，用二甲硫醚还原得到相应的醛。当这些醛与无机酸反应时，以良好的产率得到呋喃酮。另一方面，用膦酰基乙酸三乙酯处理醛，该醛易于由1，2：5，6-二-O-异丙基吡啶-D-甘露醇通过氧化制备， 关于我们 以高产率得到α，β-不饱和酯。不饱和酯经氢化二异丁基铝还原，再与原乙酸三乙酯和对苯二酚发生Claisen重排反应，高产率地得到β-乙烯基酯。以Hageman's酯为起始原料，经4-乙氧羰基-3-甲基-2-环己烯-1-酮（Hageman's酯）合成了蓝绿皂苷元A的A，B环。Hageman酯与乙二醇在对甲苯磺酸存在下于乙苯中反应得到缩酮酯，其中双键异构化到3，4-位。然后用活性MnO_2在CH_2Cl_2中氧化得醛，再用Ph_3P = CH_2在苯中氧化得4-乙烯基-3-甲基-3-环己烯-1-一个缩醛。该烯烃与某些亲双烯体（乙炔二甲酸二乙酯、马来酸酐）进行Diels-Alder反应的多次尝试均未获得良好的结果。少

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 … More 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. Less