DISULFIDE STEREOCHEMISTRY - CONFORMATIONS AND CHIROPTICAL PROPERTIES OF L-CYSTINE DERIVATIVES
DISULFIDE STEREOCHEMISTRY - CONFORMATIONS AND CHIROPTICAL PROPERTIES OF L-CYSTINE DERIVATIVES
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DOI：
10.1021/ja00772a036
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发表时间：
1972-01-01
影响因子：
15
通讯作者：
MARTIN, RB
中科院分区：
文献类型：
--
作者：
CASEY, JP;MARTIN, RB
L-胱氨酸的连续N-甲基化(L-CySSCy(1))逆转了各时亚甲基氢从二甲基半胱氨酸转变为四甲基半胱氨酸时邻近偶合常数和化学位移的相对大小。这些PMR结果表明，最稳定的抗硫和羧酸盐残基为1的交错乙基微乳剂被具有抗硫和甲基化铵基团的旋转异构体所取代。对于同一系列化合物，在>；240 nm处的二硫键吸收的复合圆二色谱(CD)在N-甲基化时从负号变为正号，允许估计由于不对称中心对二硫键发色团的扰动而导致的每个旋转体对旋光性的贡献。当从水和甲醇转移到较长链的醇类溶剂时，1的烷基酯二盐酸盐的二硫键CD也从负号变为正号，这表明旋转体的选择性也发生了类似的变化。1的酰化和酰胺化对邻位偶联常数和Cd的影响很小，说明这些取代基对旋转异构体的分布影响很小。混合二硫化物如L-CySSC2H5的屈服偶联常数和CD曲线类似于1。这些结果表明，内环相互作用对1的构象没有明显的限制。1及其衍生物在溶液中具有较高的旋光性质不是由于内环相互作用，也不是由于二硫键上螺链的偏置，而是由于三个交错的旋转体数量不相等所致。从考试(-)-(9S，10S)-？Ra？S-六氢-2，3-苯二硫醚和1的晶体，在二面角小于90的情况下，一个负的长波CD符号与M的二硫键手性有关。证明了长波CD在确定二硫键的手性和监测自然产生的环五肽畸形蛋白A的构象变化中的作用。
Successive N-methylation of L-cystine (L-CySSCy (1)) reverses the relative magnitudes of the vicinal coupling constants and chemical shifts of the anisochronous methylene hydrogens on passing from di-to tetra-methylcystine. These pmr results indicate that the most stable staggered ethanicrotamer with anti sulfur and carboxylate residues for 1 is succeeded by the rotamer with anti sulfur and methylated ammonium groups. For the same series of compounds, the composite circular dichroism (CD) of the disulfide absorption at> 240 nm changes sign from negative to positive upon N-methylation, permitting estimation of contributions to optical activity by each rotamer due to perturbation of the disulfide chromophore by the asymmetric centers. Upon passing from water and methanol to longer chain alcoholic solvents, the disulfide CD of alkyl ester dihydrochlorides of 1 also changes sign from negative to positive, suggesting a similar change in rotamer preference. Acylation and amidation of 1 produce onlyminor effects on vicinal coupling constants and CD, indicating only small influences of these substituents on rotamer distribution. Mixed disulfides such as L-CySSC2H5 yield coupling constants and CD curves similar to that of 1. These results among others indicate no significant restriction on the conformation of 1 due to endocyclic interactions. The relatively high optical rotatory properties of 1 and derivatives in solution are due not to endocyclic interactions nor to biasing of screw sense in the disulfide bond but rather to unequal populations of threestaggered rotamers. From an examination of (—)-(9S, 10S)-? ra «s-hexahydro-2, 3-benzodithiin and crystals of 1, a negative long wavelength CD sign is associated with M disulfide chirality for dihedral angles less than 90. The utility of the long wavelength CD in assigning M disulfide chirality and monitoring conformational changes is demonstrated for the naturally occurring cyclopentapeptide malformin A.