绿色合成开启螺噻唑烷的药用魔力总结:螺旋支架(三)

2023-08-22 20:08:00, 砌小智 工号006 上海皓鸿生物医药科技有限公司


前言

近年来,绿色化学成为研究热点。绿色合成追求环保高效,其中,一类“双环”化合物引起广泛关注——螺噻唑烷,作为具有全方位药物活性的特殊类杂环结构,在人工合成领域可谓应用广泛。本文将介绍螺-噻唑烷的绿色合成方法,涵盖了多组分反应、环境友好型等绿色合成方法。


我们前期公众号文章《上市药物分子螺环支架合成思路总结:螺旋环支架(二)》,介绍了相关螺旋化合物的合成路线。

生物活性

螺噻唑烷类化合物在药物化学中具有重要的地位,在过去八年中显示出的抗菌、抗癌、抗糖尿病、抗氧化和抗结核等广泛的药物活性。

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合成路线

1. 微波辅助合成

Scheme 1 Synthesis of spiro-arylidene derivatives

Scheme 2 Synthesis of spiro-[indole-thiazolidines]

Scheme 3 Synthesis of diverse spirocyclic thiazolidinediones

2. 离子液体辅助合成

Scheme 4 Synthesis of fluorinated spiro[indole-thiazolidiones]

3. 固体支持的酸催化合成

Scheme 5 The production of new spiro[indoline-3,2′-thiazolidine]-2,4′-diones

Scheme 6 The feasible mechanism for the production of spiro-thiazolidin-4-ones by MCM-SO3H


4. 水相合成

Scheme 7 Production of spiro[acenaphthylene-1,2′[1,3]-thiazolidine]-2,4′(1H)-dione derivatives


Scheme 8 Plausible mechanism for the creation of spiro[acenaphthylene-1,2′[1,3] thiazolidine]-2,4′(1H)-dione derivatives

Scheme 9 Synthesis of 5-chlorospiro[indoline-3,2-thiazolidine]-2,4-dione


5.纳米催化剂辅助合成

Scheme 10 Synthesis of spiro-thiazolidinethione from naphthol Mannich bases

Scheme 11 The plausible mechanism for synthesis of spiro-thiazolidinethiones

Scheme 12 Synthesis of spiro[indeno[1,2-b]quinoxaline-[11,2′]-thiazolidine]-4′-ones


Scheme 13 Proposed mechanism for the formation of thiazolidine-4''ones derivatives

Scheme 14 Green one-pot, three-component asymmetric 1,3-dipolar cycloaddition catalyzed by the CCMFe2O4@l-proline MNRs catalyst

Scheme 15 Synthesis of spiro-thiazolidinethione from naphthol Mannich bases


6. 不对称合成

Scheme 15 Asymmetric synthesis of highly functionalized spirothiazolidinone tetrahydroquinolines


7. 杂项合成

Scheme 16 Synthesis of sugar-fused spiro-chromanono thiolizidines

Scheme 17 Synthesis of 3′-aminofluorene-9-spiro-5′-imidazolidine-2′,4′-dithione

Scheme 18 Synthesis of [5-oxo-4-(4-substituted aryl hydrazono)-3-trichloro methyl-4,5-dihydro-pyrazol-1-yl]-acetic acid ethyl ester

Scheme 19 Construction of thiazolidine-2,4-dione linked 1,2,3- triazole derivatives

Scheme 20 The plausible mechanism for the regio- and stereo-selective formation of thiazolidine-2,4-dione linked 1,2,3- triazole derivatives

Scheme 21 Synthesis of 2-arylidine-1-thia-4-azaspiro[4.5]decan-3-ones

Scheme 22 Synthesis of dispiro oxindole–pyrrolizine–thiazolidine-2,4-dione hybrids


结束语

本文旨在展示螺-噻唑烷在绿色合成领域的的重要性,并突出其多样化的合成策略。通过绿色合成的方法,我们可以以更加环保和可持续的方式合成这些化合物,为制药行业提供高效、广谱的药物候选化合物。


参考文献

Surbhi Dhadda , Shaily Sharma , Prakash Jakhar , Himanshu Sharma. Contemporary progress in the green synthesis of spiro-thiazolidines and their medicinal significance: a review. RSC Adv., 2023, 13, 3723–3742.


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