Synthesis of enantiopure carbohydrate mimetics by Lewis acid catalyzed rearrangement of 1,3-dioxolanyl-substituted 1,2-oxazines
Synthesis of enantiopure carbohydrate mimetics by Lewis acid catalyzed rearrangement of 1,3-dioxolanyl-substituted 1,2-oxazines
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DOI：
10.1002/anie.200501127
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Reissig, HU
中科院分区：
文献类型：
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作者：
Al-Harrasi, A;Reissig, HU
对映体纯的3，6-二氢-2H-1，2-恶嗪可以通过锂化的烷氧基联烯与醛硝酮的[3+ 3]环化反应容易地获得，[1]是立体选择性合成一系列高度官能化化合物的通用中间体。所有这些产品，包括多羟基化吡咯烷，立体定向的氨基多元醇和取代的四氢呋喃衍生物，[2]都是令人感兴趣的，因为它们具有潜在的生物活性，例如，作为糖苷酶抑制剂。[3]当试图用刘易斯酸将1，2-恶嗪顺式-3脱保护时，我们发现以中等产率发生重排为四氢吡喃桥连的双环1，2-恶嗪4（方案1）。[2b]由此，将syn-3的丙酮化合物保护基团并入产物4中。本文中我们报道：·该反应通常以适当取代的3，6-二氢-2H-1，2-恶嗪为起始原料进行，·所得对映体纯的双环产物可以立体选择性地转化为许多多羟基化的氨基取代的吡喃衍生物，·以类似的方式，高度官能化的氧杂环庚烷衍生物是可获得的。所得产物可以被认为是碳水化合物模拟物，[4]它们是合成生物活性化合物（例如寡糖类似物）的潜在重要构件。锂化的烷氧基丙二烯1与d-甘油醛衍生的硝酮2的立体分散加成以优异的产率产生顺式或反式构型的3（方案1）。[1]Unex-
Enantiomerically pure 3, 6-dihydro-2H-1, 2-oxazines, which are easily available by [3+ 3] cyclization of lithiated alkoxyallenes with aldonitrones,[1] are versatile intermediates for the stereoselective synthesis of a range of highly functionalized compounds. All these products, including polyhydroxylated pyrrolidines, stereodefined amino polyols, and substituted tetrahydrofuran derivatives,[2] are interesting because of their potential biological activities, for example, as glycosidase inhibitors.[3] While trying to deprotect 1, 2-oxazine syn-3 with Lewis acids we found that a rearrangement to tetrahydropyran-bridged bicyclic 1, 2-oxazine 4 occurred in moderate yield (Scheme 1).[2b] Thereby the acetonide protecting group of syn-3 was incorporated into product 4. Herein we report that:• this reaction proceeds quite generally with suitably substituted 3, 6-dihydro-2H-1, 2-oxazines as starting materials,• the obtained enantiopure bicyclic products can be converted stereoselectively into numerous polyhydroxylated amino-substituted pyran derivatives,• in a similar manner, highly functionalized oxepane derivatives are accessible.The resulting products may be regarded as carbohydrate mimetics,[4] which are potentially important building blocks for the synthesis of biologically active compounds, for example, oligosaccharide analogues. The stereodivergent addition of lithiated alkoxyallene 1 to the d-glyceraldehyde-derived nitrone 2 gives either syn-or anti-configured 3 in excellent yield (Scheme 1).[1] The unex-