呋喃法合成维生素 D 类似物。钙三醇 A 环和 1α-羟基-3-去氧维生素 D(3)的合成。

Furan approach to vitamin D analogues. Synthesis of the A-ring of calcitriol and 1α-hydroxy-3-deoxyvitamin D(3).

机构信息

Department of Chemistry, Lafayette College, Easton, Pennsylvania 18042, USA.

出版信息

J Org Chem. 2010 Oct 15;75(20):6820-9. doi: 10.1021/jo101155c.

DOI:10.1021/jo101155c

Abstract

The A-rings of calcitriol (1α,25-dihydroxyvitamin D(3)) and 1α-hydroxy-3-deoxyvitamin D(3) were synthesized using the furan approach. The critical steps in the synthesis of the A-ring of calcitriol involved an asymmetric carbonyl-ene reaction of 3-methylene-2,3-dihydrofuran with 3-(tert-butyldimethylsiloxy)propanal, a diastereoselective Friedel-Crafts hydroxyalkylation, an oxidation of the 2,3-disubstituted furan to give a γ-hydroxybutenolide, and a Peterson olefination. The A-ring (Z)-dienol of calcitriol was synthesized in 12 steps from 3-(tert-butyldimethylsiloxy)propanal in 17% yield.

摘要

采用呋喃法合成了钙三醇（1α,25-二羟基维生素 D(3)）和 1α-羟基-3-去氧维生素 D(3)的 A 环。钙三醇 A 环合成的关键步骤包括 3-亚甲基-2,3-二氢呋喃与 3-（叔丁基二甲基甲硅烷基）丙醛的不对称羰基-ene 反应、立体选择性 Friedel-Crafts 羟烷基化反应、2,3-取代呋喃的氧化生成γ-羟基丁烯内酯以及 Peterson 烯烃化反应。钙三醇的 A 环（Z）-二烯醇是由 3-（叔丁基二甲基甲硅烷基）丙醛经 12 步反应以 17%的产率合成的。

相似文献

1

Furan approach to vitamin D analogues. Synthesis of the A-ring of calcitriol and 1α-hydroxy-3-deoxyvitamin D(3).

J Org Chem. 2010 Oct 15;75(20):6820-9. doi: 10.1021/jo101155c.

2

New convergent synthesis of 1alpha,25-dihydroxyvitamin D3 and its analogues by Suzuki-Miyaura coupling between A-ring and C,D-ring parts.

J Org Chem. 2003 Dec 12;68(25):9767-72. doi: 10.1021/jo0353435.

3

Synthesis and biological activity of 22-oxa CD-ring modified analogues of 1alpha,25-dihydroxyvitamin D3: cis-perhydrindane CE-ring analogues.

Bioorg Med Chem Lett. 2004 Aug 2;14(15):3885-8. doi: 10.1016/j.bmcl.2004.05.067.

4

Synthesis of novel analogues of 1alpha,25-dihydroxyvitamin D(3) with side chains at C-18.

J Org Chem. 2004 Jul 9;69(14):4615-25. doi: 10.1021/jo0498664.

5

Efficient synthesis of novel 1alpha-amino and 3beta-amino analogues of 1alpha,25-dihydroxyvitamin d(3).

J Org Chem. 2003 Feb 7;68(3):1154-7. doi: 10.1021/jo026474t.

6

Asymmetric catalytic ene-cyclization approach to 2-fluoro-19-nor-1,25-dihydroxyvitamin D(3) A-ring analog with significant transactivation activity.

Chirality. 2001 Jul;13(7):366-71. doi: 10.1002/chir.1046.

7

New 1alpha,25-dihydroxy-19-norvitamin D3 compounds of high biological activity: synthesis and biological evaluation of 2-hydroxymethyl, 2-methyl, and 2-methylene analogues.

J Med Chem. 1998 Nov 5;41(23):4662-74. doi: 10.1021/jm9802618.

8

Functionalization at C-12 of 1alpha,25-dihydroxyvitamin D(3) strongly modulates the affinity for the vitamin D receptor (VDR).

Org Lett. 2003 Jun 26;5(13):2291-3. doi: 10.1021/ol034632c.

9

Synthesis and biological activity of 22-oxa CD-ring modified analogues of 1alpha,25-dihydroxyvitamin D3: spiro[5.5]undecane CF-ring analogues.

Bioorg Med Chem Lett. 2004 Aug 2;14(15):3889-92. doi: 10.1016/j.bmcl.2004.05.058.

10

Synthesis and structure-activity relationships of TEI-9647 derivatives as Vitamin D3 antagonists.

J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):31-4. doi: 10.1016/j.jsbmb.2004.03.046.

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍。

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

文档翻译

学术文献翻译模型，支持多种主流文档格式。