Asymmetric synthesis of (+)-loline, a pyrrolizidine alkaloid from rye grass and tall fescue
Asymmetric synthesis of (+)-loline, a pyrrolizidine alkaloid from rye grass and tall fescue
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DOI：
10.1039/b103936a
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Yokochi, AFT
中科院分区：
文献类型：
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作者：
Blakemore, PR;Kim, SK;Yokochi, AFT
(+)-洛林(1)是通过分子内[4+2]环加成25或26的酰基亚硝二烯作为关键步骤合成的。原位使用的酰基亚硝酸钠是由相应的异羟肟酸17和24氧化得到的，这些异羟肟酸是由葡萄糖经9醛或更多直接从(S)-苹果酸(18)制备。内二氢恶嗪27和29与它们的外立体异构体混合后，通过还原N-O键断裂和再作环转化为吡咯烷34和35。后者在(DHQD)(2)苯丙氨酸的存在下进行夏普莱斯氨羟化反应，得到50和它的区域异构体51。对甲苯磺酰胺50的N-甲基化，然后醇52的甲基化和伽马-内酰胺53与硼烷的还原，得到了吡咯里西丁54。对甲氧基苄基醚的裂解和随后的55热处理导致分子内醚化得到N-甲苯磺酰基洛林(57)。N-对甲苯磺基残基的最终还原裂解生成(+)-洛林，其特征是其二盐酸盐。
(+)-Loline (1) was synthesized via a pathway that employed intramolecular [4 + 2] cycloaddition of an acylnitrosodiene, 25 or 26, as a key step. The acylnitrosodienes, which were used in situ, were obtained by oxidation of the corresponding hydroxamic acids, 17 and 24, and these were prepared from either glucose via aldehyde 9 or more directly from (S)-malic acid (18). The endo dihydrooxazines 27 and 29, obtained in a mixture with their exo stereoisomer, were transformed by reductive N-O bond cleavage and reannulationinto pyrrolizines 34 and 35. The latter was subjected to Sharpless aminohydroxylation in the presence of (DHQD)(2)PHAL to give 50 along with its regioisomer 51. N-Methylation of tosyl amide 50, followed by mesylation of alcohol 52 and reduction of the gamma -lactam 53 with borane, afforded pyrrolizidine 54. Cleavage of the p-methoxybenzyl ether and subsequent thermal treatment of 55 resulted in intramolecular etherification to yield N-tosylloline (57). Final reductive cleavage of the N-tosyl residue produced (+)-loline,characterized as its dihydrochloride.