Enantioselective and Protecting Group-Free Synthesis of 1-Deoxythionojirimycin, 1-Deoxythiomannojirimycin, and 1-Deoxythiotalonojirimycin

Abstract

1-Deoxythioglyconojirimycins were synthesized by using a protecting group-free strategy, starting from readily available carbohydrates, in good overall yield. Use of benzyltriethylammonium tetrathiomolybdate, [BnEt(3)N](2)MoS(4), as a sulfur transfer reagent and borohydride exchange resin (BER) reduction of a lactone enabled the efficient synthesis of the title compounds.

Ammonium tetrathiomolybdate as a water-soluble and slow-release hydrogen sulfide donor

“…14,15 As an excellent copper chelator, TTM has been used therapeutically in the treatment of copper toxicosis, especially for Wilson’s disease. 16 It was previously noted that under strong acidic condition (5% H 2 SO 4 ) H 2 S could be generated from TTM.…”

Design and synthesis of glycomimetics: Recent advances

“…Several methodologies have been developed for the preparation of thiosugars . Among the most recent examples, a general one‐pot synthesis of thiosugars 64 by double nucleophilic displacement from various alditol precursors 65 (with xylo‐, ribo‐, manno‐, gluco‐, galacto‐, and fuco‐configurations) was reported by Zhang et al (Figure A).…”

Deoxythiosugar Derivatives with Furano, Pyrano, and Septano Motifs from L‐Gulono‐1,4‐lactone and D‐Glycero‐D‐gulo‐heptono‐1,4‐lactone

“…The mixture was filtered, and the filtrate was concentrated in vacuo to give the crude product. = 1.475 g cm -3 ; Mo-K α radiation (λ = 0.71073 Å); μ = 3.7.00 mm -1 ; 2θ = 2.9-23.0°; of 8316 reflections collected, 1123 were independent [R(int) = 0.0413]; refinement method full-matrix least-squares on F 2 , 109 refined parameters, absorption correction SADABS software, Bruker, 1996; T min = 0.8376 and T max = 0.9642; GooF = 1.063, R 1 = 0.0413, wR 2 = 0.0244 [σ Ͼ 2σ(I)]; absolute structure parameter: -0.09 (9); residual electron density: 0.169/-0.106 e Å -3 . 5:8.5) 6-Bromo-2,3,6-trideoxy-L-threo-hex-2-enono-1,4-lactone (13): [11] Butenolide 10 (4.13 g, 0.17 mol) was stirred with HCl (1 m in methanol; 110 mL, 0.11 mol) at 5°C for 2 d. The reaction mixture was then concentrated in vacuo at 30°C to give bromoalcohol 13 (3.28 g, 96 %) as a gummy solid that was pure, and that was used in further reactions.…”

“…IR (neat): ν = 1780, 1349, 1192, 1156, 1065, 1042, 893, 866 cm -1 9 Hz, 1 H, -CHOCO-), 6.18 (dd, J = 5.6, 1. After completion of the reaction, HBr was added to precipitate AgBr.…”

“…[8] However, a more general and efficient synthesis of thiosugars from carbohydrates is required in contemporary organic synthesis. After our recent success in the enantiospecific synthesis of 1-deoxy-thio-nojirimycin, 1-deoxythio-mannono-nojirimycin, and 1-deoxy-thio-talono-nojirimycin, [9] we became interested in the development of a general approach to the construction of various deoxythiosugars mimicking furanoses, pyranoses, and septanoses, starting from aldonolactones. In this paper, we describe a short and versatile enantiospecific synthesis of deoxythiosugars with thiofuranose, thiopyranose, and thioseptanose structures, starting from commercially available aldono-lactones, l-gulono-1,4-lactone (5) and d-glucoheptono-1,4-lactone (22).…”