3291-62-1

Upstream product

• 865-47-4 potassium tert-butylate 
• 535-11-5 Ethyl 2-bromopropionate 
• 67-64-1 acetone 
• 535-13-7 2-chloro-propanoic acid, ethyl ester 

Downstream Products

• 563-80-4 3-methyl-butan-2-one 
• 1384071-30-0 C₁₃H₁₈O₃S 

Relevant academic research and scientific papers

The macrocycle of leinamycin imparts hydrolytic stability to the thiol-sensing 1,2-dithiolan-3-one 1-oxide unit of the natural product

Reaction of cellular thiols with the 1,2-dithiolan-3-one 1-oxide moiety of leinamycin triggers the generation of DNA-damaging reactive intermediates. Studies with small, synthetic analogues of leinamycin reveal that the macrocyclic portion of the natural product imparts remarkable hydrolytic stability to the 1,2-dithiolan-3-one 1-oxide heterocycle without substantially compromising its thiol-sensing property.

Synthetic Approaches towards the Novel 1,3-Dioxo-1,2-dithiolane Moiety in the Antitumour Antibiotic Substance Leinamycin

A number of complementary synthetic approaches to the β-thiolactone intermediate 9 for elaboration to the novel 1,3-dioxo-1,2-dithiolane moiety 6 found in the antitumour antibiotic substance leinamycin 1 are described.Thus, deprotection of the benzylthio ether produced from 3-methylbut-2-enoic acid and toluene-α-thiol, leads to the mercapto acid 12 which on cyclisation produces the thiolactone 13. α-Methylation of the thiolactone 13, followed by α-oxygenation then gives rise to the substituted β-thiolactone 9.The β-thiolactone 9 is also produced when: (i) thesodium glycidate 17 is stirred with sodium sulfide leading to 18, followed by thiolactonisation; (ii) thioacetone is treated with the ketene derived from 2-acetoxypropanoyl chloride; and (iii) by irradiation of 3-methyl-2-trimethylsilyloxybut-2-ene 22 with thiophosgene leading to 23, followed by hydrolysis.The β-thiolactone 9 is then converted in three steps into the 1,3-dioxo-1,2-dithiolane 6 by: (i) ring opening to the thioic acid 15, using hydrogen sulfide-triethylamine; (ii) ring closure of 15 to 8 in the presence of aqueous ferric chloride; and finally (iii) oxidation using dimethyldioxirane.Treatment of the ethyl glycidate 19 with disodium disulfide in hot ethanol for 3 days provides the 1,2-dithiolane 8 directly, but in low yields (11-15percent).When the aforementioned reaction sequences are translated to the glycidate 24, derived from 4-methylcyclohex-3-enone and α-chloropropanoic acid, the syntheses of the key intermediates 25, 27 and 26 en route to the spiro-fused 1,3-dioxo-1,2-dithiolane 7 and leinamycin 1 (see Scheme 1) were secured.

Biosynthesis of Valine and Isoleucine: Synthesis and Biological Activity of (2S)-&α-Acetolactic Acid (2-Hydroxy-2-methyl-3-oxobutanoic Acid), and (2R)- and (2S)-&α-Acetohydroxybutyric Acid (2-Ethyl-2-hydroxy-3-oxobutanoic Acid)

Stereoisomers of the two substrates for the enzyme reductoisomerase of the valine-isoleucine pathway of biosynthesis have been synthesised in optically pure form.These compounds are (2S)-α-acetolactate (2-hydroxy-2-methyl-3-oxobutanoate) and (2R)- and (2S)-α-acetohydroxybutyrate (2-ethyl-2-hydroxy-3-oxobutanoate).The synthesis of (2S)-α-acetolactate represents the first synthesis in optically pure form of the substrate of the enzyme in the valine pathway.Only the (2S)-isomers of these compounds acted as substrates for the reductoisomerase of Salmonella typhimurium.

Total synthesis of swazinecic acid dilactone. Part 1. Synthesis of 2-hydroxy-2-methyl-3,5-dimethylenehexanedioic acid as an intermediate

2-Hydroxy-2-methyl-3,5-dimethylenehexanedioic acid (8) was synthesised in two ways: (a) by condensation of diethyl malonate with ethyl 3-bromomethyl-2-ethoxycarbonyloxy-2-methylbut-3-enoate followed by hydrolysis and a Mannich reaction with dimethylamine-formaldehyde, and (b) by an organocopper coupling reaction with ethyl 3-bromomethyl-2-methyl-2- trimethylsilyloxybut-3-enoate and lithium α-ethoxycarbonylvinyl(hex-1- ynyl)-cuprate followed by hydrolysis.