PARTIAL SYNTHESIS OF VINBLASTINE-TYPE ALKALOIDS
PARTIAL SYNTHESIS OF VINBLASTINE-TYPE ALKALOIDS
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DOI：
10.1039/c39750000670
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发表时间：
1975-01-01
影响因子：
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通讯作者：
GUERITTE, F
中科院分区：
文献类型：
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作者：
POTIER, P;LANGLOIS, N;GUERITTE, F
已从长春花中分离出几种抗肿瘤生物碱，其中 1 两种，长春花碱 (1) 和长春新碱 (2) 在临床上广泛使用。合成这些化合物的尝试尚未成功；如图7所示，虽然已经获得了在C(16') 3~6~8处具有“非天然”构型的化合物，但它们没有表现出显着的抗肿瘤活性。迄今为止的所有尝试均包括将文多灵 (3) 与 seco-16, 21-长春花碱衍生物，即通过长春花碱 (5) 的还原裂解获得的 16-碳乙氧基裂解胺 (4) 偶联。然而，由于在自然界中，长春花碱型生物碱很可能通过长春花碱 (3) 与合适的长春花碱（或 20-羟基长春花碱）衍生物而不是与 seco-16, 21 化合物直接偶联而形成，因此我们现在设计了这些在 C (16') 处具有“天然”构型的二聚吲哚生物碱的新部分合成。
SEVERAL antitumour alkaloids have been isolated from Catharanthus voseus, 1 two of them, vinblastin (1) and vincristine (2) being widely used clinically. Attempts2-s to synthesize these compounds have not yet been successful; 7 and although compounds possessing the'non-natural'configuration at C (16') 3~ 6~ 8 have been obtained, they have shown no significant antitumour activity. All attempts so far have consisted of coupling vindoline (3) with a seco-16, 21-catharanthine derivative, ie 16-carbornethoxycleavamine (4), obtained by reductive cleavage of catharanthine (5). However, since in Nature vinblastinetype alkaloids could well be formed through a direct coupling of vindoline (3) with a suitable catharanthine (or 20-hydroxycatharanthine) derivative rather than with a seco-16, 21 compound, we have now devised a new partial synthesis of these dimeric indole alkaloids having a'natural'configuration at C (16').