An abiotic strategy for the enantioselective synthesis of erythromycin B
An abiotic strategy for the enantioselective synthesis of erythromycin B
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DOI：
10.1002/anie.200351136
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发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Martin, SF
中科院分区：
文献类型：
--
作者：
Hergenrother, PJ;Hodgson, A;Martin, SF
(计划4)。[13]在BF3·OEt2存在下，15与丁基斯坦烷反应得到16[14]，收率为84%，其他非对映异构体加合物的混合物约为12%。我们简要地探讨了通过一些不同的醛反应将剩余的碳原子引入15的可能性，但这些努力并没有产生大量所需的加合物。然后它继续氧化末端CÀC双键生成C1羧酸。在之前的工作中，我们已经开发了两步和三步方案来实现这种转化，[6,10]但我们发现，使用最近开发的有机金属臭氧分解程序将16氧化为17提供了一种有效的一步替代方案在精心定义的条件下，通过氢解去除C13羟基上的保护基团，得到不稳定的羟基酸，然后根据山口方案进行环化，得到18.b[17]然后在C6羟基上去保护19，我们之前通过五个步骤将其转化为红霉素B(2)，从而完成了红霉素B的合成(2)。[6]总之，我们已经完成了一种新的红霉素B的合成，使用非生物策略，其中一个关键步骤是糖基化的二酸衍生物的环化。因此，该合成代表了首次通过在大内酯化步骤之前附加糖残基的方法制备天然存在的大环内酯类抗生素。此外，由17衍生的羟基酸的环化能力清楚地表明，在环化步骤中，主链的结构灵活性比以前认识到的要大
(Scheme 4).[13] The reaction of 15 with crotylstannane in the presence of BF3· OEt2 then furnished 16 [14] in 84% yield, together with about 12% of a mixture of other diastereomeric adducts. We briefly explored the possibility of introducing the remaining carbon atoms into 15 through a number of different aldol reactions,[15] but these efforts did not yield significant quantities of the desired adduct. It then remained to oxidize the terminal CÀC double bond to generate the C1 carboxylic acid. In previous work, we had developed two-and three-step protocols for effecting this transformation,[6, 10] but we found that the oxidation of 16 to give 17 by using a recently developed procedure for organometallic ozonolysis provided an efficient one-step alternative.[16] Removal of the protecting group from the C13 hydroxy function by hydrogenolysis under carefully defined conditions gave an unstable hydroxy acid, which was then cyclized according to the Yamaguchi protocol to furnish 18.[17] Deprotection of the hydroxy group at C6 then delivered 19, which we had previously converted in five steps into erythromycin B (2), thereby completing a synthesis of erythromycin B (2).[6]In conclusion, we have completed a novel synthesis of erythromycin B by using an abiotic strategy in which a key step is the cyclization of a glycosylated seco-acid derivative. As such, this synthesis represents the first time that a naturally occuring macrolide antibiotic has been prepared through an approach in which a sugar residue is appended prior to the macrolactonization step. Moreover, the ability to cyclize the hydroxy acid derived from 17 clearly illustrates that more structural flexibility in the backbone can be tolerated in the cyclization step than was previously recognized.[3]