SELECTIVE REDUCTION OF AMIDE CARBONYL GROUP IN DIPEPTIDES BY BORANE
SELECTIVE REDUCTION OF AMIDE CARBONYL GROUP IN DIPEPTIDES BY BORANE
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DOI：
10.1021/jo00869a041
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发表时间：
1976-01-01
影响因子：
3.6
通讯作者：
THOMPSON, RM
中科院分区：
文献类型：
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作者：
ROESKE, RW;WEITL, FL;THOMPSON, RM
酰胺被硼烷2.3容易还原，这使我们尝试还原N-烷氧羰基二肽酯1中的肽羰基，以获得相应的二氨基酯2。在酯水解和新生成的氨基适当保护后，产物可被视为二氨基酸4的衍生物，并可被掺入合成肽中。这将相当于通过氨基亚乙基单元（-CONH->>-CH 2NH-）选择性地置换肽键，并且将在肽激素的结构-活性研究中有用。由于BH 3还原分离的羰基的相对容易程度是-CO2 H>-CONR 2> CONHR>-CONH 2>-CO2 R> ROCONHR，2-4，因此，有可能选择性地还原1中的酰胺键。然而，位于酰胺上的酯基比分离的酯更容易还原成相应的醇。因此，当苯甲酰甘氨酸乙酯与硼烷反应时，氨基酯和氨基醇的产率分别为11%和85%。3我们发现，在-20 ℃下，用2摩尔BH 3反应4-5小时，二肽中酯的同时还原最小化。在这些条件下，有相当数量的起始原料保持未反应，但它很容易从基本产物中分离出来，并且不会大大降低该过程的合成有用性。因此，在上述条件下还原3.0 g Boc-Gly-Leu-OMe 5，在通过硅胶色谱法与其它产物分离后，得到1.24 g原料和0.64 g纯2a。碱水解2a得到氨基酸4a，产率为73%。一般来说，反应条件越强，得到的混合物（TLC）越复杂，其中只有氨基醇3能被分离出来。
The facile reduction of amides by borane2· 3 led us to at-tempt the reduction of the peptide carbonylgroup in N-alkoxycarbonyl dipeptide esters 1 in order to obtain the corresponding diamino esters 2. The products, after hydrolysis of the ester and suitable protection of the newly generated amino group, can be regarded as derivatives of diamino acids 4 and could be incorporated into synthetic peptides. This would amount to selective replacement of a peptide bond by an aminoethylene unit (-CONH-»-CH2NH-) and would be useful in structure-activity stud-ies in peptide hormones. The amino group also offers a point of attachment of a reactive group for affinity labeling of enzymes and receptors.Since therelative ease of reduction of isolated carbonyl groups by BH3 is-C02H>-CONR2> CONHR>-CONH2>-C02R> ROCONHR, 2-4 it was a priori possible to reduce selectively the amide bond in 1. However, an ester'group located a to an amide is more easily reduced to the corresponding alcohol than is an isolated ester. Thus when benzoyl glycineethyl ester was treated with borane, the amino ester and amino alcohol were produced in yields of 11 and 85%, respectively. 3 We have found that concurrent reduction of the ester in dipeptides is minimized by carrying out the reaction at-20 C with 2 mol of BH3 for 4-5 h. Under these conditions, a considerable amount of starting material remains unreact-ed, but it is easily separated from the basic products and does not diminish greatly the synthetic usefulness of the procedure. Thus, reduction of 3.0 g of Boc-Gly-Leu-OMe5 under the above conditions gave 1.24 g of starting material and 0.64 g of pure 2a, after separation from other products by chromatography on silica gel. Alkaline hydrolysis of 2a gave the amino acid 4a in 73% yield. In general, more vigor-ous reaction conditions ledto more complex mixtures (TLC) from which onlythe amino'alcohols 3 could be iso-lated.