158585-09-2

Upstream product

• 16534-12-6 3,5-dihydroxy-4-bromobenzoic acid 
• 100-39-0 benzyl bromide 

Downstream Products

• 1012334-99-4 C₂₂H₂₈O₅ 
• 1254733-82-8 benzyl 2,6-bis(benzyloxy)-4'-fluorobiphenyl-4-carboxylate 
• 171564-80-0 (3R,4R)-3-(4-Benzyloxy-benzoylamino)-4-[3,5-bis-benzyloxy-4-(2-benzyloxycarbonyl-benzoyl)-benzoyloxy]-azepane-1-carboxylic acid benzyl ester 
• 171564-83-3 (3R,4R)-3-Benzoylamino-4-[3,5-bis-benzyloxy-4-(2-benzyloxy-6-benzyloxycarbonyl-benzoyl)-benzoyloxy]-azepane-1-carboxylic acid benzyl ester 
• 171564-81-1 (3R,4R)-3-(4-Benzyloxy-benzoylamino)-4-[3,5-bis-benzyloxy-4-(2-benzyloxy-benzoyl)-benzoyloxy]-azepane-1-carboxylic acid benzyl ester 
• 171564-73-1 2-[2,6-Bis-benzyloxy-4-(tert-butyl-diphenyl-silanyloxymethyl)-benzoyl]-benzoic acid benzyl ester 
• 171564-76-4 (2-Benzyloxy-phenyl)-[2,6-bis-benzyloxy-4-(tert-butyl-diphenyl-silanyloxymethyl)-phenyl]-methanol 

Relevant academic research and scientific papers

Total Synthesis of 3-Oxo- and 3β-Hydroxytauranin via Negishi Coupling of a Bis(ortho-oxy)-Functionalized Benzyl Chloride

The first asymmetric synthesis of the sesquiterpene quinones 3-oxo- and 3β-hydroxytauranin (1, 2) was achieved and the originally proposed structure of 3α-hydroxytauranin was revised. The protected benzyl chloride 5 was obtained in six steps starting from 4-bromo-3,5-dihydroxybenzoic acid (8) via a highly scalable approach. The troublesome Negishi coupling of the benzyl chloride 5 with alkenyldimethylalane 6 was optimized to furnish all-trans-farnesylarene 14 in very good yield. This prenylated arene was transformed in six additional steps to 3β-hydroxytauranin (2). Finally, a new convenient access to propargylated terpenes without using dry cryogenic ammonia and gaseous allene or propyne is described. The first total synthesis of the sesquiterpene quinones 3-oxo- and 3β-hydroxytauranin (2) was achieved and the originally proposed structure of 3α-hydroxytauranin was revised. The key step of the synthesis is the Negishi coupling of the bis(ortho-oxy)-functionalized benzyl chloride 5 with the alkenyldimethylalane 6.

Optimizing glucokinase activator binding kinetics to lower in vivo hypoglycemia risk

Activation of glucokinase represents a promising strategy for the treatment of type 2 diabetes; however, drug candidates have failed in clinical trials due to narrow therapeutic index between glucose-lowering efficacy and hypoglycemia. Described herein is a novel strategy for the design of next generation glucokinase activators with increased therapeutic index, which involves the optimization of activator-enzyme binding kinetics (kon, k off). This approach is based on the idea that activator binding kinetics are relevant to pharmacodynamics since the affinity of activator binding to glucokinase is cooperative with glucose such that, the rate at which an activator dissociates may influence the enzyme's sensitivity to changes in physiological glucose concentrations. This study provides a compelling example of using fast-off binding kinetics for developing safe and effective activator drugs targeting glucokinase.

SUBSTITUTED SPIROCYCLIC AMINES USEFUL AS ANTIDIABETIC COMPOUNDS

Substituted spirocyclic amines of structural formula I are selective antagonists of the somatostatin subtype receptor 5 (SSTR5) and are useful for the treatment, control or prevention of disorders responsive to antagonism of SSTR5, such as Type 2 diabetes, insulin resistance, lipid disorders, obesity, atherosclerosis, metabolic syndrome, depression, and anxiety.

Total synthesis of (-)· and (+)-balanol

Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described. In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-∈-caprolactam.

Total Synthesis of Balanol and Designed Analogues

The total synthesis of balanol, a potent protein kinase C inhibitor isolated from the fungus Verticillium balanoides, is described.The hexahydroazepine fragment was prepared from D-serine through a sequence of reactions including the diastereoselective allylboration of a derived amino aldehyde and a base-induced 7-exo-tet ring closure as key steps.The benzophenone fragment was secured through the initial coupling of the two functionalised aromatic components through an ester linkage, followed by intramolecular nucleophilic attack of an aryl lithium derivative to form the desired ketone bridge.After coupling of the two balanol domains, the adoption of benzyl-derived protecting groups for the latent functionalities then allowed the liberation of balanol in a single step by catalytic hydrogenolysis.Finally, the newly developed synthetic strategy was applied to the synthesis of a variety of designed balanol analogues for biological evaluation. - Keywords: antitumor agents, balanol, enzyme inhibitor, natural product, total synthesis

Total Synthesis of (-)-Balanol

(-)-Balanol, a fungal metabolite with potent protein kinase C inhibitory properties, has been prepared in a total synthesis which makes use of an anionic homo-Fries rearrangement approach to the benzophenone subunit and in which the azepane subunit is obt