88981-35-5Relevant articles and documents
Bispalladacycle Catalyzed Nucleophilic Enantioselective Allylation of Aldehydes by Allylstannanes
Frey, Wolfgang,Heberle, Martin,Legendre, Sarah,Peters, René,Wannenmacher, Nick,Weber, Manuel
, (2022/03/08)
Enantiopure homoallylic secondary alcohols are very important synthetic building due to the versatility of the hydroxyl and olefin moieties. A key strategy to prepare them is by nucleophilic allylation of aldehydes. A large number of catalyst concepts emerged that allow for high enantioselectivity. Still, in many target-oriented syntheses of complex structures stoichiometric methods are preferred over catalytic ones. The need for high catalyst loadings and long reaction times, plus unsatisfying reproducibility and substrate scopes are reasons for that. In the present study we report the first palladium catalysts capable of controlling asymmetric nucleophilic allylations of aldehydes with allyltributyltin. TONs up to 620 were achieved, which is significantly higher than for any other reported catalyst. The method is also tolerating electronically and sterically unfavorable substrates. We show that a transmetallation occurs, favoring an η1-allyl coordination mode with the bispalladacycles. In contrast, for the corresponding monopalladacycle an unproductive η3 coordination is dominant.
Development of a Practical, Biocatalytic Synthesis of tert-Butyl (R)-3-Hydroxyl-5-hexenoate: A Key Intermediate to the Statin Side Chain
Chen, Fener,Hu, Chen,Huang, Zedu,Liu, Minjie,Yue, Xiaoping
supporting information, p. 1700 - 1706 (2020/10/26)
The HMG-CoA reductase inhibitors, statins, are one of the most effective and bestselling cholesterol-lowering drugs. The use of statins has greatly extended people's lives and improved the quality of their life. Development of a more efficient, stereoselective, and sustainable synthesis of statins is continuingly of utmost importance. In the present study, through screening of ketoreductases (KREDs) and reaction optimization, we have successfully performed a highly stereoselective reduction of ketoester 1a catalyzed by KRED-06 at a pilot-plant scale without the addition of exogenous NADP+, generating 3.21 kg of enantiomerically pure tert-butyl (R)-3-hydroxyl-5-hexenoate ((R)-2a) (96.2% yield, >99.9% enantiomeric excess (ee)). This newly developed biocatalytic process alleviates the cryogenic conditions (-40 °C) employed in our first-generation synthesis of (R)-2a using NaBH4 and (l)-tartaric acid. Coupled with our previously established synthesis of bromocarbonate 3a via a one-pot diastereoselective carboxylation/bromocyclization of (R)-2a, we have developed an innovative, practical synthesis route to statin side chain, possessing great potential to be implemented into industrial production of statins.
Synthesis, conformation, and biological activities of a des-a-ring analog of 18-deoxy-aplog-1, a simplified analog of debromoaplysiatoxin
Ashida, Yoshiki,Yanagita, Ryo C.,Kawanami, Yasuhiro,Okamura, Mutsumi,Dan, Shingo,Irie, Kazuhiro
, p. 942 - 957 (2019/08/01)
10-Me-Aplog-1 as a simplified analog of tumor-promoting debromoaplysiatoxin and a potent activator of protein kinase C (PKC) is a promising chemotherapeutic agent. In this study, we synthesized a des-A-ring analog (4) of 18-deoxy-aplog-1 as a syntheticall
