TOTAL SYNTHESIS OF BLEOMYCIN A(2) AND RELATED AGENTS .4. SYNTHESIS OF THE DISACCHARIDE SUBUNIT - 2-O-(3-O-CARBAMOYL-ALPHA-D-MANNOPYRANOSYL)-L-GULOPYRANOSE AND COMPLETION OF THE TOTAL SYNTHESIS OF BLEOMYCIN A(2)
TOTAL SYNTHESIS OF BLEOMYCIN A(2) AND RELATED AGENTS .4. SYNTHESIS OF THE DISACCHARIDE SUBUNIT - 2-O-(3-O-CARBAMOYL-ALPHA-D-MANNOPYRANOSYL)-L-GULOPYRANOSE AND COMPLETION OF THE TOTAL SYNTHESIS OF BLEOMYCIN A(2)
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DOI：
10.1021/ja00092a014
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发表时间：
1994-06-29
影响因子：
15
通讯作者：
HONDA, T
中科院分区：
文献类型：
--
作者：
BOGER, DL;HONDA, T
详细介绍了2-O-(3-O-carbamoyl-alpha-D-mannopyranosyl)-L-gulopyranose的化学合成及其与易于制备结构类似物的博莱霉素A(2)(1)的全合成的结合。该方法的关键战略元素包括erythro-N-alpha-CBZ-N-pi-trityl-beta-hydroxy-L-histidine甲酯与六乙酰2-O-(3-O-carbamoyl-alpha-D-mannopyranosyl)-L-gulopyranose的β-糖基二苯基磷酸酯的非对映选择性α-O-糖苷化，以提供4(63%)个糖基氯立体化学的干净反转。随后将4融合到博莱霉素A(2)(1)中是通过与四肽S(94%)和N-α-BOC-嘧啶布拉米酸(83%)顺序偶联完成的，这两种四肽都在没有修饰功能保护的情况下以极高的产率进行。3，4，6-三-O-苄基-β-L-古吡喃糖苷(31)与3-O-carbamoyl-2，4，6-tri-O-acetyl-alpha-D-mannose(19)的α-糖基二苯基磷酸酯(19)发生非对映选择性糖苷反应，得到前体二糖2和3，产率为93%，保留了α-D-甘露糖氯的立体化学。以D-甘露糖为原料，通过2，3-O-二丁基锡烯的区域选择性C3醇烷基化反应制备了D-甘露糖和L-甘露糖衍生物19和31，用于1-4的合成。28通过非对映选择性Rh(I)催化的氢硼化反应转化C5立体化学，将D-甘露糖简单地相互转化为L-古糖衍生物，为制备31提供了关键转化。
The chemical synthesis of 2-O-(3-O-carbamoyl-alpha-D-mannopyranosyl)-L-gulopyranose and its incorporation into a total synthesis of bleomycin A(2) (1) readily adaptable to the preparation of structural analogs are detailed. Key strategic elements of the approach include diastereoselective alpha-O-glycosidation of erythro-N-alpha-CBZ-N-pi-trityl-beta-hydroxy-L-histidine methyl ester with the beta-glycosyl diphenyl phosphate of hexaacetyl 2-O-(3-O-carbamoyl-alpha-D-mannopyranosyl)-L-gulopyranose to provide 4 (63%) with clean inversion of the glycosyl Cl stereochemistry. The subsequent convergent incorporation of 4 into bleomycin A(2) (1) was accomplished through sequential couplings with tetrapeptide S (94%) and N-alpha-BOC-pyrimidoblamic acid (83%), both of which proceeded in exceptionally high yield without protection of the adorning functionality. The precursor disaccharides 2 and 3 were obtained in a diastereospecific glycosidation of benzyl 3,4,6-tri-O-benzyl-beta-L-gulopyranoside (31) with the alpha-glycosyl diphenyl phosphate of 3-O-carbamoyl-2,4,6-tri-O-acetyl-alpha-D-mannose (19), which proceeded in exceptionally good yield (93%) with net retention of the alpha-D-mannopyranosyl Cl stereochemistry. Both the suitably protected D-mannose and L-gulose derivatives 19 and 31 for incorporation into 1-4 were prepared from D-mannose with implementation of a regioselective equatorial C3 alcohol alkylation of the 2,3-O-dibutylstannylene derived from 13 and 23. A tactically simple interconversion of a D-mannose to L-gulose derivative through inversion of the C5 stereochemistry by diastereoselective Rh(I)-catalyzed hydroboration of 28 provided the key transformation for the preparation of 31.