213838-14-3

Upstream product

• 213838-12-1 (1R,2S,3R)-3-Methyl-cyclohexane-1,2-dicarboxylic acid 1-methyl ester 
• 67-56-1 methanol 
• 15433-46-2 (+/-)-3t-methyl-cyclohexane-1r,2c-dicarboxylic acid-anhydride 
• 100-51-6 benzyl alcohol 
• 213979-99-8 (1R,2S,3R)-3-Methyl-cyclohexane-1,2-dicarboxylic acid dimethyl ester 

Downstream Products

• 213838-15-4 (1S,2R,6R)-2-Amino-6-methyl-cyclohexanecarboxylic acid methyl ester 

Relevant academic research and scientific papers

Enantioselective Synthesis of (-)-Pumiliotoxin C from a Chiral Amino Ester and an Acetylenic Sulfone that Acts as an Alkene Dipole Equivalent

A new synthesis of the naturally occurring (-)-enantiomer of the dendrobatid alkaloid pumiliotoxin C (1) was achieved by the conjugate addition of methyl (-)-cis-2-amino-trans-6-methylcyclohexanecarboxylate (3) to 1-(p-toluenesulfonyl)-1-pentyne (4), followed by intramolecular acylation to afford (4aS,5R,8aR)-4a,5,6,7,8,8a-hexahydro-5-methyl-2-propyl-3-(p-toluenesulfonyl)-4- quinolinone(2). The acetylenic sulfone thus acts as the synthetic equivalent of an alkene dipole species. The required enantiopure amino ester 3 was obtained by an approach based on pig liver esterase (PLE)-mediated hydrolysis. Thus, the (-)- and (+)-enantiomers of racemic dimethyl trans-3-methylcyclohexane-cis,cis-1,2-dicarboxylate (6) afforded the corresponding half-esters 7 and 8, respectively, when treated with PLE. The desired half-ester 7 was recovered intact after selective conversion of the free carboxylic acid group of the byproduct 8 into its benzyl ester. Half-ester 7 was converted into enantiopure (-)-6 with diazomethane, followed by regioselective saponification and Curtius rearrangement to afford the required enantiopure key intermediate 3. Finally, hydrogenation of the enol triflate of enaminone 2, followed by reductive desulfonylation, afforded the product (-)-1.

Efficient asymmetric synthesis of unnatural β-amino acids

The simple and highly enantioselective methanolysis of cyclic meso-anhydrides mediated by cinchona alkaloids leads to a broad variety of dicarboxylic acid mono-methyl esters with up to 99% ee. From these products, unnatural N-protected β-amino esters can be obtained by means of Curtius degradation of the corresponding acyl azides. Subsequent cleavage of the protecting groups leads to the free β-amino acids in excellent yields. By enantiomer differentiating opening of racemic anhydrides, synthetically highly useful regioisomeric amino acid esters become readily available.