Total synthesis of L-biopterin from L-tartaric acid via 5-deoxy-L-arabinose
Total synthesis of L-biopterin from L-tartaric acid via 5-deoxy-L-arabinose
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DOI：
10.1021/jo961426s
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发表时间：
1996-11-29
影响因子：
3.6
通讯作者：
Duhamel, L
中科院分区：
文献类型：
--
作者：
Fernandez, AM;Duhamel, L
L生物蝶呤(Biopterin，1)是由Patterson等人从人体尿液中分离得到的一种植物生长因子，是天然蝶类化合物中分布最广的化合物之一。1通过其5，6，7，8-四氢形式，在苯丙氨酸转化为酪氨酸2和酪氨酸转化为DOPA，3在黑色素合成，4和色氨酸羟化中发挥重要的酶辅助因子的作用。5因此，四氢生物蝶呤已被开发为治疗中枢神经系统疾病的药物，如苯丙酮尿症、帕金森氏症和阿尔茨海默病以及抑郁症。6自Patterson等人首次合成L生物蝶呤(1)以来，已经报道了几个合成方法，其中8-13个是由VisContini的团队完成的。8其中，8，9 L-鼠李糖和L-阿拉伯糖是合成关键中间体5-脱氧-L-阿拉伯糖的主要原料(2)。10最近，以较便宜的(S)-乳酸乙酯11或D-核糖12为原料，合成了具有吸引力的L生物蝶呤，关键中间体是5-脱氧-L-核糖(5-脱氧-L-阿拉伯糖的C2中的同分异构体(2))。L生物蝶呤(1)也是由三氨基丁氧基嘧啶与2-甲酰氧杂环己烷缩合而成。本文介绍了以L-酒石酸(3)为原料合成5-脱氧-L-阿拉伯糖(2)的新途径，提高了合成效率和经济性。我们认为2，3-二羟基-4-甲基丁内酯(4)可能是2的一个很好的前驱体。
L-Biopterin (1), one of the most ubiquitous compounds in the class of the naturally occurring pterins, was isolated from human urine as a growth factor of Crithidia fasciculata by Patterson et al. 1 Through its 5, 6, 7, 8-tetrahydro form, 1 functions as an essential enzyme cofactor in the conversion of phenylalanine to tyrosine2 and tyrosine to DOPA, 3 in melanine synthesis, 4 and in tryptophan hydroxylation. 5 As a consequence, tetrahydrobiopterin has been developed as a remedy for central nervous system diseases such as phenylketonuria, Parkinson’s and Alzheimer’s diseases, and depression. 6 Since the first synthesis of L-biopterin (1) by Patterson et al., 7 several syntheses have been reported, 8-13 especially by Viscontini’s group. 8 In most of those, 8, 9 L-rhamnose and L-arabinose are the starting materials to the key intermediate, 5-deoxy-L-arabinose (2). 10 More recently, novel attractive syntheses of L-biopterin were described, employing less expensive ethyl (S)-lactate11 or D-ribose12 as starting materials; the key intermediate is then 5-deoxy-L-ribose (epimer in C2 of 5-deoxy-L-arabinose (2)). L-Biopterin (1) was also prepared by condensation of triaminobutoxypyrimidine with 2-formyloxiranes. 13In this paper, we describe a new synthetic access to 5-deoxy-L-arabinose (2) that employs L-tartaric acid (3) as starting material and thus improves both efficiency and economy. We thought that 2, 3-dihydroxy-4-methylbutyrolactone (4) could be an excellent precursor of 2. The retrosynthesis is presented in Scheme 1. This strategy relies on the condensation of 2, 5, 6-triamino-4-