Synthesis of Biologically Active Nitrogen Containing Aliphatic Compounds Using Nitroethanol as a Synthon.

使用硝基乙醇作为合成物合成具有生物活性的含氮脂肪族化合物。

• 批准号: 01571140
• 负责人: NAKAGAWA Masako
• 金额: $ 1.34万
• 依托单位: Faculty of Pharmaceutical Sciences, Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01571140/
• 关键词: nitroethanol; nitroaldol reaction; ceramides; cerebroside B1a; chiral synthesis; pseudodistomins; (+)-erythro-N-lauroyldocosasphinga-4, 8-dienine; sialidase inhibitor; 095-acetamido-4-hydroxypipecolinic acid; 10absolute configuration; セレブロサイドB_1

A novel types of biologically active nitrogen containing compounds have been synthesized via the nitroaldol reaction using nitroethanol by our recently developed method as shown below.1. Synthesis of Cerebroside B1a, 1aSynthesis of four diastereoisomeric ceramides including the aglycone cerebroside B1a, 1a, was achieved, one of which was converted to the optically active 1a by glycosylation. Consequently, the absolute configuration of 1a was determined to be (2S,3R,4E,8Z,2'R)-1-0-(beta-D-glucopyranosyl)-N-(2'-hydr-hexadecanoyl)-4, 8-sphingadienine.2. Synthesis of (+)-erythro-N-lauroyldocosasphinga-4, 8-dienine, 2.The racemic 2 was synthesized by the simple method developed by the total synthesis of 1a. Optical resolution gave (+) and (-)-2. We also synthesized the optically active 2 by two different chiral synthesis.3. Synthetic approaches to the pseudodistomins A (3a) and B (3b) novel antineoplastic piperidine alkaloids with calmodulin antagonistic activity from the Okinawan Tunicate Pseudodistoma KanokoWe have established the synthesis of the piperidine ring which has the requisite three substitutents at the proper position by three different approaches.4. Sialidase inhibitor, 5-acetamido-4-hydroxypipecolinic acid 4The compound 4 was synthesized by analogous method used for the synthesis of 3.

我们最近开发的方法以硝基乙醇为原料，通过硝基醛反应合成了一类新的具有生物活性的含氮化合物。合成了四种非对映异构体神经酰胺，包括脑苷元B1a， 1a，其中一种通过糖基化转化为具有旋光性的1a。因此，确定1a的绝对构型为(2S,3R,4E,8Z,2' r)-1-0-（β - d -葡萄糖吡喃基）- n -（2'-羟基十六烷基）- 4,8 -鞘脂二烯2。（+）-红- n -月桂酰基羟基沥青- 4,8 -二烯胺的合成外消旋体2是由1a的全合成发展起来的简单方法合成的。光学分辨率为（+）和(-)-2。我们还通过两种不同的手性合成方法合成了旋光性2。从冲绳岛被囊动物中提取的具有钙调素拮抗活性的新型抗肿瘤胡椒碱生物碱A （3a）和B （3b）的合成方法通过三种不同的方法合成了在适当位置上具有三个取代基的胡椒碱环。唾液酸酶抑制剂5-乙酰氨基-4-羟基酚酸4采用合成3的类似方法合成了化合物4。

项目成果

S.Kodato: "Synthesis of Cerebroside B1b with Antiulcerogenic Activity I Synthesis of Ceramides with Optically Active α-Hydroxy-palmitic Acids" Tetrahedron. 45. 7247-7264 (1989)

S.Kodato：“具有抗溃疡活性的脑苷脂 B1b 的合成 I 与光学活性 α-羟基棕榈酸的神经酰胺的合成”四面体。 7247-7264 (1989)

M.Nakagawa: "Total Synthesis of(-)-erythro-N-lauroyl-docosasphingga-4,8-dienine from anemonia sulcata and Determination of the absolute configuration." J.Chem.Soc.,Chemical Communications. (1990)

M.Nakakawa：“从苏卡达海葵中全合成（-）-赤式-N-月桂酰-二十二碳二烯酸-4,8-​​二烯并确定绝对构型。”

T.Hino: "2-Hydroxy-1-substitued-1,2,3,4-tetrahydro-β-carbolines.The Pictet-Spengler Reaction of N-Hydroxytryptamine with Aldehydes." Chem.Pharm.Bull.38. 59-64 (1990)

T.Hino：“2-羟基-1-取代的-1,2,3,4-四氢-β-咔啉。N-羟基色胺与醛的 Pictet-Spengler 反应。Chem.Pharm.Bull.38。” 64（1990）

Masako NAKAGAWA: "Total Synthesis of (+)ーerythroーNーLauroylー docosasphingaー4,8ーdienine from Anemonia sulcata and Determination of the Absolute Configuration" Jurnal of Chemical Society,Chemical Communications,. 603-605 (1990)

Masako NAKAGAWA：“来自苏卡达海葵的(+)－erythroN－Lauroy－docosasphinga－4,8－二烯的全合成和绝对构型的测定”化学学会杂志，化学通讯，603-605（1990）。

Masako NAKAGAWA, Akihiko Tsuruoka, Jun YOSHIDA, and Tohru HINO: "Total Synthesis of (+)-erythro-N-Lauroyldocosasphinga-4, 8-dienine from Anemonia sulcata and Determination of the Absolute Configuration" Journal of Chemical Society, Chemical Communications

Masako NAKAGAWA、Akihiko Tsuruoka、Jun YOSHIDA 和 Tohru HINO：“来自海葵的 ( )-erythro-N-Lauroyldocosasphinga-4, 8-dienine 的全合成和绝对构型的测定”化学会杂志，化学通讯