196495-55-3

Upstream product

• 149125-61-1 methyl 4-(benzyloxy)-2-butynoate 
• 91142-50-6 4-benzyloxy-2-butyn-1-ol 
• 375384-84-2 methyl (Z)-4-benzyloxy-3-iodobut-2-enoate 

Downstream Products

• 1154594-03-2 (E)-3-benzyloxymethyl-5-phenyl-2-penten-4-yn-1-ol 
• 375384-96-6 6-((Z)-4-benzyloxy-3-iodobut-2-en-1-yl)-3-isobutoxy-6-methylcyclohex-2-en-1-one 
• 375384-94-4 6-((Z)-4-benzyloxy-3-iodobut-2-en-1-yl)-3-isobutoxycyclohex-2-en-1-one 
• 375385-05-0 4-((Z)-4-benzyloxy-3-iodobut-2-en-1-yl)-4-methylcyclohex-2-en-1-one 
• 375385-02-7 4-((Z)-4-benzyloxy-3-iodobut-2-en-1-yl)cyclohex-2-en-1-one 
• 561067-72-9 methyl 6-(methoxymethoxy)-4-(benzyloxy)methyl-2E,4E-hexadienoate 
• 561067-71-8 (Z)-1-benzyloxy-2-iodo-4-(methoxymethoxy)-2-butene 
• 375384-88-6 (Z)-1-benzyloxy-4-bromo-2-iodobut-2-ene 

Relevant academic research and scientific papers

Synthesis and evaluation of colletoic acid core derivatives

Cortisol homeostasis has been linked to the pathogenesis of metabolic syndrome (MetS), since it stimulates hepatic gluconeogenesis and adipogenesis. MetS is classified as a constellation of health conditions that increase the risk of type 2 diabetes and cardiovascular disease. Intracellular cortisol levels are regulated by 11β-hydroxysteroid dehydrogenase (type 1 and type 2) in a tissue dependent manner. The type 1 enzyme (11β-HSD1) is widely expressed in glucocorticoid targeted tissues and is responsible for the conversion of cortisone to the active cortisol. Local reduction of cortisol regeneration presents a potential strategy for MetS treatment. Recently we disclosed the total synthesis of (+)-colletoic acid as a potent 11β-HSD1 inhibitor. Herein, we describe our improved processing chemistry for the synthesis of the colletoic acid core to access a diverse number of derivatives for evaluation against 11β-HSD1. The Evan's chiral auxiliary was utilized to construct the acyclic precursor 12 to afford the acorane core 9 using a modified Heck reaction in excellent chemical yields. The colletoic acid core derivatives showed modest activity against 11β-HSD1 and will serve for further biological evaluation.

Preparation of perhydroisoquinolines via the intramolecular Diels-Alder reaction of N-3,5-hexadienoyl ethyl acrylimidates: A formal synthesis of (±)-reserpine

The intramolecular Diels-Alder reaction of N-3,5-hexadienoyl ethyl acrylimidates provides an efficient method for the synthesis of cis-fused hexahydroisoquinolones. As a demonstration of the stereochemical control offered by this cycloaddition, two approaches to the construction of the DE rings of reserpine are reported. In the second entry, N-((4-(trimethylsilyl)ethoxymethoxy)methyl- 6-benzyloxy-3Z, 5E-hexadienoyl)-1-aza-2-ethoxy-1,3-butadiene (40) undergoes cycloaddition to produce as the major product (4aS*,7R*,8aS*)-7-benzyloxy-5-((2-trimethylsilyl) ethoxymethoxy)methyl-3,4,4a,7,8,8a-hexahydroisoquinol-3-one (41). Cycloadduct 41 is then stereospecifically elaborated to (4aS*,5S*,6R*,7R*,8aR*)-6-methoxy-5- methoxycarbonyl-7-(3,4,5-trimethoxy)benzoyldecahydroisoquinoline-2-carboxylic acid methyl ester (3), a key intermediate previously transformed to reserpine.

Intramolecular conjugate addition of alkenyl and aryl functions to enones initiated by lithium-iodine exchange

Equation presented Treatment of each of the substrates 20-26, 29, and 46-48 with t-BuLi in THF, in the presence of HMPA and TMSCI, provides good-to-excellent yields of the intramolecular conjugate addition products 30-36, 37, and 49-51, respectively.