ALKALOID BIOSYNTHESIS .6. BIOSYNTHESIS OF COLCHICINE
ALKALOID BIOSYNTHESIS .6. BIOSYNTHESIS OF COLCHICINE
复制标题
DOI：
10.1039/jr9640004257
复制
发表时间：
1964-01-01
期刊：
影响因子：
--
通讯作者：
BINKS, R
中科院分区：
文献类型：
--
作者：
BATTERSBY, AR;REYNOLDS, JJ;BINKS, R
如果上述想法大致正确，[2- 14 C]酪氨酸的活性应该主要集中在秋水仙碱的6位，并且开发了生物碱的降解以分离该碳原子。对秋水仙碱本身的试验表明，将托酚酮系统转化为稳定的苯型核是有利的。因此，秋水仙碱通过Fernholtz 16的方法转化为别秋水仙碱（11; R= CO，H），已知16 * 17的重排明确地伴随着碳原子9的挤出而发生。然后用重氮甲烷甲基化得到别秋水仙碱16（11; R= CO，Me）。这可以用氢化铝锂还原，根据条件，得到主要含有中性物质或主要含有碱性产物的混合物。从中性馏分中分离出醇（IV），从碱性馏分中分离出胺（111; R= OH）。对这种还原的仔细研究允许获得碱（111; R= OH）的高产率和可重复产率。在高氯酸存在下，该物质中的苄醇残留物在钯上顺利地进行氢解，得到碱（111; R= H）。这现在具有所需的稳定性，以允许尝试霍夫曼消除，第一阶段，涉及转化为季碘化物（V; X= I），用碘甲烷和碳酸钾或碱性硫酸二甲酯完成，然后加入过量的碘化钾。
If the foregoing ideas are broadly correct, activity from [2-14C] tyrosine should be concentrated largely at position 6 of colchicine, and a degradation of the alkaloid was developed to isolate this carbon atom. Trial experiments on colchicine itself showed that it would be advantageous to convert the tropolone system into a stable benzenoid nucleus. Consequently, colchicine was converted by the method of Fernholtz l6 into allocolchiceine (11; R= CO, H), a rearrangement which was known l6* l7 to occur unambiguously with the extrusion of carbon atom 9. Methylation with diazomethane then afforded allocolchicine l6 (11; R= C0, Me). This could be reduced with lithium aluminium hydride to give, depending upon the conditions, a mixture containing mainly neutral material or mainly basic products. The alcohol (IV) was isolated from the neutral fraction and the amine (111; R= OH) from the basic one. Careful study of this reduction allowed high and reproducible yields of the base (111; R= OH) to be obtained. Hydrogenolysis of the benzylic alcohol residue in this material proceeded smoothly over palladium in the presence of perchloric acid to afford the base (111; R= H). This now had the required stability to allow Hofmann elimination to be attempted, and the first stage, involving conversion into the quaternary iodide (V; X= I), was accomplished with methyl iodide and potassium carbonate or with alkaline dimethyl sulphate followed by the addition of an excess of potassium iodide.