AN UNUSUAL REARRANGEMENT OF A LITHIATED N-ACYL-TETRAHYDROISOQUINOLINE TO AN AMINO-INDAN SKELETON AND STRUCTURAL COMPARISON OF 3-AMINO-2-METHYLINDAN ACIDS AND TETRAHYDRONAPHTHALENE-2-CARBOXYLIC ACIDS AS POSSIBLE BUILDING-BLOCKS FOR PEPTIDE-TURN MIMICS
AN UNUSUAL REARRANGEMENT OF A LITHIATED N-ACYL-TETRAHYDROISOQUINOLINE TO AN AMINO-INDAN SKELETON AND STRUCTURAL COMPARISON OF 3-AMINO-2-METHYLINDAN ACIDS AND TETRAHYDRONAPHTHALENE-2-CARBOXYLIC ACIDS AS POSSIBLE BUILDING-BLOCKS FOR PEPTIDE-TURN MIMICS
复制标题
DOI：
10.1002/hlca.19930760721
复制
发表时间：
1993-01-01
影响因子：
1.8
通讯作者：
SEEBACH, D
中科院分区：
文献类型：
--
作者：
GEES, T;SCHWEIZER, WB;SEEBACH, D
锂-1-锂-6,7-二甲氧基-3-甲基-2-戊酰-1,2,3,4-四氢异喹啉-3-羧酸盐通过1,2-迁移重排为5,6-二甲氧基-2-甲基-1-（戊酰氨基）吲哚-2-羧酸的二硫代衍生物（2,[1,2]-异位位移并保留构型），类似于去质子化醚的Wittig重排（方案2）。用x射线衍射测定了重排产物的绝对构型和结构。通过将各种其他四氢异喹啉衍生物（6,7,10,15）置于金属化条件下测试重排发生的结构条件。只有另一种化合物被发现经历了相同的重排（15 - bbb16）。讨论了重排的可能机制（B-G）。由于四取代c原子的存在，印度型β -氨基酸衍生物2具有构象锁定结构（N-C-C-CO2R二面角44°）。为了比较，我们制备了相应的四毒素型β -氨基酸衍生物19-22，通过x射线分析（对酯21）表明，这些衍生物具有较大的二面角（约60度）。有人提出，这里描述的类型的β -氨基酸可以并入肽，沿着肽主链提供已知角度的弯曲。
Lithium 1-lithio-6,7-dimethoxy-3-methyl-2-pivaloyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate rearranges to the dilithio derivative of 5,6-dimethoxy-2-methyl-1-(pivaloylamino)indan-2-carboxylic acid (2, [1,2]-sigmatropic shift with retention of configuration) by 1,2-migration resembling the Wittig rearrangement of deprotonated ethers (Scheme 2). The structure, including absolute configuration of the rearrangement product, was determined by X-ray diffraction. Structural conditions for the rearrangement to occur are tested by subjecting various other tetrahydroisoquinoline derivatives (6, 7,10, 15) to the metalating conditions. Only one other compound was found to undergo the same rearrangement (15 --> 16). Possible mechanisms of the rearrangement are discussed (B-G). Due to the presence of a tetrasubstituted C-atom, the indan-type beta-amino-acid derivative 2 has a conformationally locked structure (N-C-C-CO2R dihedral angle 44-degrees). For comparison, the corresponding tetralin-type beta-amino-acid derivatives 19-22 were prepared, and it was shown by X-ray analysis (of the ester 21) that these have larger dihedral angles (ca. 60-degrees). It is proposed that beta-amino acids of the type described here could be incorporated into peptides, providing bents of known angles along the peptide backbone.