Stereoselective synthesis of meso-2,6-diaminopimelic acid and its selectively protected derivatives
Stereoselective synthesis of meso-2,6-diaminopimelic acid and its selectively protected derivatives
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DOI：
10.1021/jo972133h
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发表时间：
1998-04-03
影响因子：
3.6
通讯作者：
Vederas, JC
中科院分区：
文献类型：
--
作者：
Gao, Y;Lane-Bell, P;Vederas, JC
研究了细菌肽聚糖的关键组分meso-二氨基庚二酸（DAP）（1a）的四种选择性保护衍生物和异构体的合成路线。N-（叔丁氧羰基）-D-烯丙基甘氨酸（2）和N-（苄氧羰基）-L-烯丙基甘氨酸（4）与乙二醇酯化并通过烯烃复分解环化成2，7-二氨基辛二酸的保护衍生物7。丙烷-1，3-二醇与2和N-（苄氧基羰基）-L-乙烯基甘氨酸部分的潜在前体（例如N-（苄氧基羰基）-L-谷氨酸盐或N-（苄氧基羰基）-L-甲硫氨酸亚砜）的类似连接得到12或15，在尝试产生用于烯烃复分解成DAP衍生物的乙烯基甘氨酸前体时，这两者都产生α，β-不饱和酯14。另一条路线是在SnCl_4催化下，N-苄氧羰基-L-烯丙基甘氨酸甲酯（18）与苯基环己醇异构体的乙醛酸酯（18）进行烯化反应，得到约1.5 - 1.5 85：15比例的非对映异构醇（19或20）。这些可以在一系列步骤中转化为DAP衍生物，所述步骤采用相应甲磺酸酯的叠氮化物置换以引入第二个氮。第三种方法，包括用（S）-联萘酚-钌催化剂将纯（6S）-2-酮基-6-[N-（苄氧基羰基）氨基]庚二酸二甲酯（32）还原为相应的醇33作为关键步骤，得到79：21的异构体比。第四条路线使用双（恶唑啉）-铜络合物41作为手性催化剂，用于（S）-4-（苯硫基）烯丙基甘氨酸甲酯（39）和乙醛酸甲酯的烯反应，以94：6的异构比得到42。在存在Gbz基团的情况下，硼化镍去除硫和双键，得到所需的醇，即（2S，6S）-6-[N（苄氧羰基）氨基]-2-羟基庚烷-1，7-二酸二甲酯（33）。作为关键步骤，使用Mitsunobu转化，用N-叔丁基[[2-（三甲基甲硅烷基）乙基]磺酰基]氨基甲酸酯（34）引入所需的选择性保护的第二氮。
Four synthetic routes to selectively protected derivatives and isomers of meso-diaminopimelic acid (DAP) (1a), a key constituent of bacterial peptidoglycan, were investigated. N-(tert-butyloxycarbonyl)-D-allylglycine (2) and N-(benzyloxycarbonyl)-L-allylglycine (4) were esterified to ethylene glycol and cyclized via olefin metathesis to a protected derivative 7 of 2,7-diaminosuberic acid. Analogous linking of propane-1,3-diol with 2 and potential precursors of N-(benzyloxycarbonyl)-L-vinylglycine moieties, such as N-(benzyloxycarbonyl)-L-glutamate or N-(benzyloxycarbonyl)-L-methionine sulfoxide, gave 12 or 15, both of which produced the alpha,beta-unsaturated ester 14 upon attempted generation of the vinylglycine precursor for olefin metathesis to DAP derivatives. An alternative route, based on SnCl4-catalyzed ene reaction of methyl N-(benzyloxycarbonyl)-L-allylglycinate (18) with glyoxylate esters of phenylcyclohexanol isomers as chiral auxiliaries, gave ca. 85:15 ratios of diastereomeric alcohols (19 or 20). These could be transformed to DAP derivatives in a series of steps employing azide displacement of corresponding mesylates to introduce the second nitrogen. A third method, involving reduction of pure dimethyl (6S)-2-keto-6-[N-(benzyloxycarbonyl)amino]pimelate (32) to the corresponding alcohol 33 with (S)-binaphthol-ruthenium catalyst as the key step, gives a 79:21 isomeric ratio. The fourth route employs the bis(oxazoline)-copper complex 41 as a chiral catalyst for the ene reaction of methyl (S)-4-(phenylthio)allylglycinate (39) and methyl glyoxylate to afford 42 in 94:6 isomeric ratio. Nickel boride removal of sulfur and the double bond in the presence of the Cbz group gives the desired alcohol, dimethyl (2S,6S)-6-[N(benzyloxycarbonyl)amino]-2-hydroxyheptane-1,7-dioate (33). The required selectively protected second nitrogen is introduced using Mitsunobu inversion with N-tert-butyl [[2-(trimethylsilyl)ethyl]sulfonyl]carbamate (34) as a key step.