Fields of expertise: Synthetic organic chemistry: Organocayalysis for site-selective acylation of carbohydrates; Total synthesis of natural glycosides via sequential site-selective functionalization; Remote asymmetric induction via acylation and C-H amination; Kinetic resolution of mechanically planar chiral rotaxanes; Asymmetric induction via memory of chirality; Molecular recognition for chain-length-selective acylation and silylation.

Author details: Takeo Kawabata has been a full Professor in Department of Pharmaceutical Sciences at International University of Health and Welfare since 2021. He obtained his B.Sc. from Kyoto University, Japan, in 1978, and Ph.D. in Pharmaceutical Sciences from the same university in 1983. He was a post-doctoral fellow at Indiana University, USA, with Professor Paul A. Grieco (1983-1985), and a Research Scientist at Sagami Chemical Research Center (1985-1989). He was appointed as an Assistant Professor at Institute for Chemical Research, Kyoto University, in 1989, promoted to an Associate Professor in 1998 and a full Professor in 2004. He retired from Kyoto University in 2021, and moved to the current position. He is the author of some 200 peer-reviewed publications. He received Pharmaceutical Society of Japan Award for Young Scientists in 1996, Molecular Chirality Award in 2012, The Pharmaceutical Society of Japan Award in 2017, and The Commendation for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology in 2018.

Abstract: We have developed organocatalysts that enable to deliver acyl groups into the C(4)-OH of glucopyranosides site-selectively in the presence of the intrinsically more reactive free primary OH at the C(6).1) The salient feature of the catalysts was successfully applied to the total syntheses of several natural glycosides.

1. Multifidosides A-C2)

At the final stage of the total synthesis, catalytic site-selective introduction of the p-coumaroyl group into the desired (4)-OH of the glucose core of the precursor glycoside with five free hydroxy groups has been achieved. The conventionally difficult molecular transformation could be performed in a predictable manner due to the functional group tolerance of the site-selective acylation promoted by the organocatalysts. An advantage of this strategy may involve avoiding the risks of undesired side reactions during the removal of the protecting groups at the final step of the total synthesis.

1. Strictinin, Tellimagrandin II, and Pterocarinin C (Ellagitannin family)3,4)

Extremely short-step total synthesis of strictinin, tellimagrandin II, and pterocarinin C has been accomplished based on the unconventional retrosynthetic routes without using protective groups for starting glucose. The key reactions are the b-selective glycosidation of a gallic acid derivative using unprotected glucose as a glycosyl donor, and catalyst-controlled site-selective introduction of a galloyl group into the inherently less reactive hydroxy group in the resulting glucoside. The overall synthetic efficiency seems to be compatible with the biosynthetic pathway.

1. Punicafolin and Macaranganin  (Ellagitannin family)5)

The first total syntheses of punicafolin and macaranganin were achieved in 7 steps, respectively from naturally abundant D-glucose. The prominent features of the synthesis are i) sequential site-selective introduction of the adequate galloyl groups into the requisite hydroxy groups of D-glucose, and ii) stereodivergent construction of the 3,6-HHDP bridge from a common intermediate via the flipping process of the pyranose ring to the less stable axial-rich conformer. Because no protective groups were used for glucose throughout the process, extremely short step total syntheses were accomplished.

1. Kawabata, T. et al. J. Am. Chem. Soc. 2007, 129, 1289012895.
2. Ueda, Y. et al. Angew. Chem. Int. Ed. 2015, 54, 11966-11970.
3. Takeuchi, et al. Angew. Chem. Int. Ed. 2015, 54, 6177-6180.
4. Takeuchi, et al. Chem. Pharm. Bull., 2017, 65, 25-32.
5. Shibayama, H. et al. J. Am. Chem. Soc. 2021, 143, 1428-1434.