Total synthesis of (+)-sinefungin
Total synthesis of (+)-sinefungin
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DOI：
10.1021/jo960670g
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发表时间：
1996-09-06
影响因子：
3.6
通讯作者：
Liu, WM
中科院分区：
文献类型：
--
作者：
Ghosh, AK;Liu, WM
Sinefungin (1) 是一种从链霉菌中分离出来的核苷抗生素，由 D-核糖合成。 C-6 和 C-9 立体中心都是通过有效的不对称合成构建的。 C-6 胺立体化学是通过 (1S,2R)-1-氨基-2-茚满醇衍生的恶唑烷酮 9 的高度非对映选择性烯丙基化 (>99% de)，然后进行 11 至 12 的 Curtius 重排来设定的。 Sinefungin (1) 的 C-9 氨基酸立体化学是通过铑手性双膦催化的不对称氢化建立的。 α-(酰氨基)丙烯酸酯衍生物。发现异头乙酸酯20的混合物在C-6氨基甲酸酯NH存在下的异头腺苷化极其困难。在腺苷化反应之前，必须将 C-6 氨基甲酸酯 NH 转化为其 N-苄基衍生物 21。通过 Vorbruggen 方案，利用全甲硅烷基化的 N-G-苯甲酰腺嘌呤和三氟甲磺酸三甲基甲硅烷基，成功地进行了腺苷化。
Sinefungin (1) a nucleoside antibiotic isolated from Streptomyces has been synthesized from D-ribose. Both the C-6 and C-9 stereogenic centers were constructed by efficient asymmetric syntheses. The C-6 amine stereochemistry was set by a highly diastereoselective allylation (>99% de) of a (1S,2R)-1-amino-2-indanol-derived oxazolidinone 9 followed by a Curtius rearrangement of 11 to 12. The C-9 amino acid stereochemistry of sinefungin (1) was established by a rhodium chiral bisphosphine-catalyzed asymmetric hydrogenation of an alpha-(acylamino)acrylate derivative. The anomeric adenosylation of the mixture of anomeric acetates 20 in the presence of C-6 urethane NH was found to be extremely difficult. Conversion of the C-6 urethane NH as its N-benzyl derivative 21 was necessary prior to the adenosylation reaction. Successful adenosylation was effectively carried out by Vorbruggen's protocol utilizing persilylated N-G-benzoyladenine and trimethylsilyl triflate.