博菜黴素(bleomycin)為一種抗癌之glycopeptide抗生素，其抗腫瘤活性，主要是經由金屬離子鍵結後，在氧氣存在下，切斷核苷酸鏈。博菜黴素的分子結構可分為幾個單元，其中雙醣體在生化活性所扮演的角色是最不清楚的，如能有結構完全確定的化合物，將有助於探討glycopeptide與核苷酸的作用關係，本文即描述一簡便途徑來合成該雙醣體，包括開發新方法來製備非天然的L-式艾杜糖(idose)及異葡萄糖(gulose)。以購得之二丙酮 a-D-葡萄糖(diacetone a-D-glucose)經由兩步合成enol ether 65後，進行選擇性的硼氫化反應得到L-式艾杜糖的衍生物66，再歷經三個合成步驟合成3-O-benzyl-1,6-anhydro-b-L-gulopyranose 70，接著選擇性將碳2之立體中心反轉產生4-O-benzoyl-3-O-benzyl-1,6-anhydro-b-L-gulopyranose 72作為醣供給體(glycosyl acceptor)。另外，以購得的2,3-O-isopropylidene-1,6-anhydro-b-D-mannopyranose 57為起始物經由七個合成步驟得到6-O-Acetyl-2,4-di-O-benzyl-3-carbamoyl-D-mannopyranosyl trichloroacetimidate 79作為醣給予體(glycosyl donor)，和4-O-benzoyl-1,6-anhydro-b- L-gulopyranose 72在路易士酸催化下，醣供給體和醣接受體反應產生雙醣體80，產率為91 %，進一步進行acetolysis即可得到所要之博菜黴素雙醣體的衍生物81(95%)。

The bleomycins are a family of glycopeptide antiumor antibiotics and exhibits potent biological activity via the metal-dependent oxidative cleavage of nucleotides in the presence of oxygen. Of all the bleomycin subunits the role of carbohydrate domain is the most poorly understand. Having adequate material with well-defined structure to study the interaction between glycopeptides and nucleotides is an urgent issue. A convenient route for the synthesis of disaccharide subunit is described here, including the development of new strategy in the preparation of unnatural L-ido and L-gulo sugars. 1,2:3,5-Di-O- isopropylidene-6-deoxy-a-D-xylo-hex-5-enofuranose 65 was obtained from commercially available diacetone a-D-gulose 63 in two steps and followed by stereoselective hydroboration of enol ether 65 to generate 1,2:3,5-di-O-isopropylidene-b-L-idofuranose 66. 3-O-benzyl-1,6- anhydro-b-L-gulopyranose 70 was preparated from L-idofuranose derivative 66 in three steps and followed by selective chiral center inversion at C2 provided 4-O-benzoyl-3-O- benzyl-1,6-anhydro-b-L-gulopyranose 72 as a glycosyl aceptor. The trichloroacetimidate 79 was generated from commercially available 2,3-O-isopropylidene-1,6-anhydro-b-D- mannopyranose 57 as a glycosyl donor in seven steps. Coupling of both donor and acceptor in the presence of TMSOTf led to the disaccharide 80 in 91% yield which underwent acetolysis to afford the desired the sugar moiety 81 in 95% yield.

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