22791-80-6

Upstream product

• 4160-82-1 3,3-dimethylglutaric anhydride 
• 69120-98-5 5-Bromo-3,3-dimethylpentanoic acid 
• 53120-74-4 3,3-dimethylpent-1,5-diol 
• 111-68-2 1-Heptylamine 
• 3121-82-2 2,2-dimethylpentane-1,5-diol 
• 4839-46-7 3,3-Dimethylglutaric acid 
• 61193-04-2 3-(R,S),5-(R,S)-3,5-dicyano-4,4-dimethyl-2,6-dioxopiperidine 

Downstream Products

• 4839-46-7 3,3-Dimethylglutaric acid 
• 139878-67-4 3-(2,4-Difluoro-phenyl)-1-heptyl-1-(5-hydroxy-3,3-dimethyl-pentyl)-urea 
• 139773-03-8 N-(5-bromo-3,3-dimethylpentyl)-N'-(2,4-difluorophenyl)-N-heptylurea 
• 133871-94-0 2,3-Bis(benzyloxy)-4,4-dimethyltetrahydropyran 
• 133871-96-2 trans-2-(3'-Chlorobenzoxy)-4,4-dimethyl-3-hydroxytetrahydropyran 
• 133871-99-5 2-(Benzyloxy)-3-hydroxy-4,4-dimethyltetrahydropyran 
• 790662-04-3 6-(1-ethoxy-3-methylbuta-1,3-dienyl)-4,4-dimethyl-3,4-dihydro-2H-pyran 
• 790661-94-8 (E)-6-(1-ethoxybuta-1,3-dienyl)-4,4-dimethyl-3,4-dihydro-2H-pyran 
• 884877-05-8 4-[1-methyl-1-(N-methyl-N-phenylcarbamoyl)ethylcarbamoyl]-3,3-dimethylbutyl acetate 
• 884877-06-9 5-hydroxy-3,3-dimethyl-N-[1-methyl-1-(N-methyl-N-phenylcarbamoyl)ethyl]pentanamide 

Relevant academic research and scientific papers

Copper-Catalyzed Double Additions and Radical Cyclization Cascades in the Re-Engineering of the Antibacterial Pleuromutilin

A general synthetic sequence involving simply prepared starting materials provides rapid access to diverse, novel tricyclic architectures inspired by pleuromutilin. SmII-mediated radical cyclization cascades of dialdehydes, prepared using a new

A Total Synthesis of (±)-Ceratopicanol via Palladium Catalyzed Reductive Cyclization

An efficient total synthesis of ceratopicanol was achieved through successive Pd catalyzed reductive cycloaddition and cyclization reactions. The Pd mediated cyclization reaction to form a triquinane structure demonstrated that a small structural difference changed the reaction pathway either to form different structures or reduced non-cyclized product depending on the reaction conditions.

Copper-catalyzed enantioselective alkene carboetherification for the synthesis of saturated six-membered cyclic ethers

The enantioselective copper-catalyzed oxidative coupling of alkenols with styrenes for the construction of dihydropyrans, isochromans, pyrans and morpholines is reported. A concise formal synthesis of a σ1receptor ligand using this alkene carbo

Primary Anion–π Catalysis of Epoxide-Opening Ether Cyclization into Rings of Different Sizes: Access to New Reactivity

The concept of anion–π catalysis focuses on the stabilization of anionic transition states on aromatic π surfaces. Recently, we demonstrated the occurrence of epoxide-opening ether cyclizations on aromatic π surfaces. Although the reaction proceeded through unconventional mechanisms, the obtained products are the same as those from conventional Br?nsted acid catalysis, and in agreement with the Baldwin selectivity rules. Different mechanisms, however, should ultimately lead to new products, a promise anion–π catalysis has been reluctant to live up to. Herein, we report non-trivial reactions that work with anion–π catalysis, but not with Br?nsted acids, under comparable conditions. Namely, we show that the anion–π templated autocatalysis and epoxide opening with alcoholate–π interactions can provide access to unconventional ring chemistry. For smaller rings, anion–π catalysis affords anti-Baldwin oxolanes, 2-oxabicyclo[3.3.0]octanes, and the expansion of Baldwin oxetanes by methyl migration. For larger rings, anion–π templated autocatalysis is thought to alleviate the entropic penalty of folding to enable disfavored anti-Baldwin cyclizations into oxepanes and oxocanes.

INTEGRIN INHIBITORS

Disclosed are small molecule inhibitors of αvβ6 integrin, and methods of using them to treat a number of diseases and conditions.

Catalytic Asymmetric Synthesis of Cyclohexanes by Hydrogen Borrowing Annulations

Hydrogen borrowing catalysis serves as a powerful alternative to enolate alkylation, enabling the direct coupling of ketones with unactivated alcohols. However, to date, methods that enable control over the absolute stereochemical outcome of such a process have remained elusive. Here we report a catalytic asymmetric method for the synthesis of enantioenriched cyclohexanes from 1,5-diols via hydrogen borrowing catalysis. This reaction is mediated by the addition of a chiral iridium(I) complex, which is able to impart high levels of enantioselectivity upon the process. A series of enantioenriched cyclohexanes have been prepared and the mode of enantioinduction has been probed by a combination of experimental and DFT studies.

Discovery of a flexible triazolylbutanoic acid as a highly potent uric acid transporter 1 (URAT1) inhibitor

In order to systematically explore and understand the structure-activity relationship (SAR) of a lesinurad-based hit (1c) derived from the replacement of the S atom in lesinurad with CH2, 18 compounds (1a-1r) were designed, synthesized and subjected to in vitro URAT1 inhibitory assay. The SAR exploration led to the discovery of a highly potent flexible URAT1 inhibitor, 1q, which was 31-fold more potent than parent lesinurad (IC50 = 0.23 μM against human URAT1 for 1q vs. 7.18 μM for lesinurad). The present study discovered a flexible molecular scaffold, as represented by 1q, which might serve as a promising prototype scaffold for further development of potent URAT1 inhibitors, and also demonstrated that the S atom in lesinurad was not indispensable for its URAT1 inhibitory activity.

The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase

Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely defi ne the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine.

Synthetically useful transformations of δ-sultones and thiane-1,1-dioxides obtained by C-H insertion

δ-Sultones and thiane-1,1-dioxides that carry a carbethoxy group at α-position, easily accessible by C-H insertion, are potentially useful synthetic intermediates. Their stereoselective alkylation, rearrangement and conversion to γ-lactones have been demo

Structure-activity study of new inhibitors of human betaine-homocysteine S-methyltransferase

Betaine-homocysteine S-methyltransferase (BHMT) catalyzes the transfer of a methyl group from betaine to L-homocysteine, yielding dimethylglycine and L-methionine. In this study, we prepared a new series of BHMT inhibitors. The inhibitors were designed to mimic the hypothetical transition state of BHMT substrates and consisted of analogues with NH, N(CH3), or N(CH 3)2 groups separated from the homocysteine sulfur atom by a methylene, ethylene, or a propylene spacer. Only the inhibitor with the N(CH3) moiety and ethylene spacer gave moderate inhibition. This result led us to prepare two inhibitors lacking a nitrogen atom in the S-linked alkyl chain: (RS,RS)-5-(3-amino-3-carboxypropylthio)-3-methylpentanoic acid and (RS)-5-(3-amino-3-carboxypropylthio)-3,3-dimethylpentanoic acid. Both of these compounds were highly potent inhibitors of BHMT. The finding that BHMT does not tolerate a true betaine mimic within these inhibitors, especially the nitrogen atom, is surprising and evokes questions about putative conformational changes of BHMT upon the binding of the substrates/products and inhibitors.