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Review
. 2016;16(11):1200-16.
doi: 10.2174/1568026615666150915111741.

Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry

Minghao Feng, Bingqing Tang, Steven H Liang, Xuefeng Jiang  1
Affiliations
Review

Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry

Minghao Feng et al. Curr Top Med Chem. 2016.

Abstract

The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a broad range of pharmaceuticals and natural products. For centuries, sulfur continues to maintain its status as the dominating heteroatom integrated into a set of 362 sulfur-containing FDA approved drugs (besides oxygen or nitrogen) through the present. Sulfonamides, thioethers, sulfones and Penicillin are the most common scaffolds in sulfur containing drugs, which are well studied both on synthesis and application during the past decades. In this review, these four moieties in pharmaceuticals and recent advances in the synthesis of the corresponding core scaffolds are presented.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors confirm that this article content has no conflict of interest.

Figures

Fig. 1
Fig. 1
Representative sulfur containing scaffolds in natural products and pharmaceuticals
Fig. 2
Fig. 2
Conventional routes to sulfonamide
Fig. 3
Fig. 3
Environmentally benign sulfonamide synthesis in water.
Fig. 4
Fig. 4
Sulfonamide synthesis involving flow chemistry.
Fig. 5
Fig. 5
Cu catalyzed sulfonamide synthesis between sodium sulfinates and amines
Fig. 6
Fig. 6
Sulfonamide synthesis via a metal free oxidative coupling.
Fig. 7
Fig. 7
Fe catalyzed sulfonamide synthesis using nitroarenes as the nitrogen sources.
Fig. 8
Fig. 8
Sulfonamide synthesis using SO2 fixation protocol.
Fig. 9
Fig. 9
Sulfur dioxide mediated one-pot, three- and four-component syntheses of polyfunctional sulfonamides.
Fig. 10
Fig. 10
DABSO used instead of SO2 in sulfonamide synthesis.
Fig. 11
Fig. 11
Pd catalyzed aminosulfonylation of aryl halides using DABSO as sulfur source.
Fig. 12
Fig. 12
Pd catalyzed three-component coupling of arylboronic acids, DABSO and hydrazines.
Fig. 13
Fig. 13
Cu-catalyzed three-component reaction of triethoxysilanes, sulfur dioxide, and hydrazines.
Fig. 14
Fig. 14
Functionalized N-aminosulfonamides synthesis via free radical reactions.
Fig. 15
Fig. 15
Synthesis of aryl sulfonamides via Pd catalyzed chlorosulfonylation of arylboronic acids.
Fig. 16
Fig. 16
Synthesis of aryl thioethers via Pd catalyzed Ullman coupling.
Fig. 17
Fig. 17
Long-lived catalyst for the Pd-catalyzed coupling of aryl halides with thiols.
Fig. 18
Fig. 18
Copper-catalyzed carbon-sulfur bond formation protocol in water.
Fig. 19
Fig. 19
Fig. 19a. Intramolecular direct cross-coupling using Na2S2O3 as a sulfurating reagent. Fig. 19b. Intermolecular direct cross-coupling access to diverse aromatic sulfides using Na2S2O3 as a sulfurating reagent.
Fig. 20
Fig. 20
Fig. 20a. Cu-Catalyzed S-transfer reaction: from amines to sulfides. Fig. 20b. Cu-Catalyzed S-transfer reaction: from 1-aryltriazenes to sulfides.
Fig. 21
Fig. 21
Chan Lam-type S-arylation of thiols with boronic acids.
Fig. 22
Fig. 22
(POCOP)Rh catalyst for the coupling of aryl halides with thiols.
Fig. 23
Fig. 23
Ru catalyzed oxidation of thioethers to sulfones.
Fig. 24
Fig. 24
Pd catalyzed synthesis of ammonium sulfinates from aryl halides and DABSO.
Fig. 25
Fig. 25
Synthesis of sulfones from organozinc reagents, DABSO, and alkyl halides.
Fig. 26
Fig. 26
Synthesis of sulfones from aryldiazonium tetrafluoroborates, DABSO, and aryliodonium tetrafluoro-borates.
Fig. 27
Fig. 27
Synthesis of penicillin derivatives via light promoted radical cyclization.
Fig. 28
Fig. 28
Fig. 28a. Synthesis of penicillin derivatives via Fe(III) promoted radical cyclization. Fig. 28b. Synthesis of penicillin derivatives via Mn(III) Cu(II) promoted radical cyclization.
Fig. 29
Fig. 29
A direct approach to penams via azomethine ylide.
Fig. 30
Fig. 30
A stereoselective synthesis of optically active β-lactams from Meldrum’s acid derivatives.
See this image and copyright information in PMC

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