The Kobayashi aldol reaction has become a prominent transformation in polyketide syntheses. This methodology takes advantage of the directing effects of the Evans auxiliary and allows the stereoselective incorporation of a four carbon segment with two additional methyl branches establishing an anti-relationship between the two newly formed chiral centers. So far this transformation was restricted to anti-aldol products. We present here a modified protocol that provides the corresponding aldol product with high syn-selectivity.
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http://dx.doi.org/10.1021/ol300353w | DOI Listing |
Chemistry
October 2024
Green & Sustainable Chemistry, Social, Cooperation Laboratory, Graduate School of Science, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
An atom-economical sequential-flow synthesis of donepezil, a widely prescribed drug for Alzheimer's disease, was accomplished using inexpensive, commercially available precursors. This achievement was made possible by reconfiguring the synthetic route to include only heterogeneous catalytic addition and condensation reactions, with a particular emphasis on skeletal transformation and bond formation through hydrogenation processes. Notably, water was the sole byproduct in this synthesis.
View Article and Find Full Text PDFOrg Lett
June 2024
School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
The asymmetric total synthesis of (+)-lemnardosinane A, a rare rearranged sesquiterpenoid, has been accomplished from ()-carvone. Key features of the synthesis are the formation of a bicyclo[3.3.
View Article and Find Full Text PDFProc Jpn Acad Ser B Phys Biol Sci
October 2023
Department of Chemistry, School of Science, The University of Tokyo.
Catalytic asymmetric direct-type aldol reactions of ketones with aldehydes are a perennial puzzle for organic chemists. Notwithstanding the emergence of a myriad of chiral catalysts to address the inherent reversibility of the aldol products, a general method to access acyclic α-chiral ketones from prochiral aryl ketones has remained an unmet synthetic challenge. The approach outlined herein is fundamentally different to that used in conventional catalysis, which typically commences with an α-proton abstraction by a Brønsted base.
View Article and Find Full Text PDFChem Commun (Camb)
June 2023
School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
The first total synthesis of applanatumol A has been achieved in a highly stereocontrolled manner. The synthetic method includes assembly of the contiguous chiral centers by convergent Fráter-Seebach alkylation, construction of the seven-membered ring by intramolecular aldol reaction, and stereoselective tandem cyclization to form the tetracyclic skeleton.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
June 2023
School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
The total synthesis of lucidumone (1), a Ganoderma meroterpenoid, was accomplished in racemic form from easily prepared 6 and 7 in 10 steps as the longest linear sequence. The synthesis was completed through one-pot preparation of the tetracyclic core skeleton by Claisen rearrangement followed by an intramolecular aldol reaction. The intramolecular aldol reaction allowed for the stereocontrolled construction of the bicyclo [2.
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