SYNTHETIC STUDIES OF STEROID DERIVATIVES CONTAINING 9-MEMBERED LACTONE

白藜芦素A是中药白术的成分之一，是一种13，14：14，15-双孕酮类化合物，具有呋喃并呋喃环和9元内酯环。最近，我们发展了环烯丙基硫叶立德的化学，并通过重氮硫化物生成的环烯丙基硫叶立德的S型重排反应，找到了一种高效合成官能化(β-乙烯-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，我们研究了蓝绿色配基A的呋喃并[2，3-b]呋喃环的合成。重排产物δ-取代-β-乙烯-δ-内酯被臭氧氧化，生成的臭氧与二甲基硫醚还原得到相应的醛。当这些醛用无机酸处理时，以较好的产率得到呋喃酮类化合物。另一方面，醛的处理，容易从1，2：5，6-二-O-异丙基丙二烯-D-甘露醇通过氧化，与三乙基膦酸膦…更多的α，β-不饱和酯产率较高。用二异丁基氢化铝还原不饱和酯，再与原乙酸三乙酯和对苯二酚进行克莱森重排反应，得到高产率的β-乙烯基酯。用80%的盐酸-80%甲醇处理得到β-乙烯基-γ-羟甲基-γ-内酯，产率适中。在对甲苯磺酸的存在下，在回流苯中，Hageman酯与乙二醇反应得到缩酮，其中的双键异构化为3，4-位。乙酯在四氢呋喃中与LiAlH4还原，然后在CH2Cl2中与活性MnO2氧化得到醛。在苯中用ph3p=CH2反应生成4-乙烯基-3-甲基-3-环己烯-1-酮缩醛。这种烯烃与一些亲二烯化合物(乙二酸二乙酯、顺丁烯二酸酐)进行了多次Diels-Alder反应，但都没有得到满意的结果。较少

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