Stereocontrolling Effect of a Single Triisopropylsilyl Group in 1,2-Cis-Glucosylation

Session: 
PS2 Poster session 2 Even numbers
Code: 
P116
Location (hall): 
Foyer
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15
Leonid
Kononov

Polina Abronina1, Nelly Malysheva1, Alexander Zinin1, Natalia Kolotyrkina1Leonid Kononov1

1N.D. Zelinsky Institute Of Organic Chemistry, Moscow, Russian Federation

Many naturally occurring biologically important glycoconjugates contain 1,2-cis-linked glucose. Stereoselective 1,2-cis-glucosylation with benzyl protected glycosyl donors is usually achieved by fixation of the conformation of the glycosyl cation by a cyclic protective group at O-4 and O-6 [1], remote participation of acyl groups [2] and with the use of other methods. 

It is important to note that synthetic routes circumventing hydrogenolysis step, often used for removal of benzyl protecting groups, are especially attractive for preparation of glycoconjugates containing 1,2-cis-linked glucose and unsaturated moieties in the aglycon. At the same time, examples of investigations of 1,2-cis-glucosylation with the use of benzyl-free glucosyl donors are limited. In contrast to the known methods for controlling glycosylation stereochemistry, we assumed that a similar fixation of the conformation of the glycosyl cation could be achieved by introducing the bulky TIPS group at O-2. This hypothesis is indirectly supported by our previously published results on the use of TIPS group at O-2 of a glycosyl donor for stereoselective 1,2-cis-glycosylation in the synthesis of D-arabinofuranosides [3], D-galactopyranosides [4] and L-fucopyranosides [5, 6]. 

Herein we report comparison of the results of α-D-glucosylation using 2-O-TIPS, 2,3-di-O-TIPS substituted thioglucosides with remote O-acyl groups and 2-O-TIPS substituted thioglucosides containing the rigid 4,6-O-benzylidene cycle. We found that the use of more reactive 2,3-di-O-TIPS derivative, which adopts 1C4 chair conformation, led to the anomeric mixture, while the use of corresponding 2-O-TIPS substituted derivatives, which exist in normal 4C1 chair conformation, is 1,2-cis-stereoselective. We observed that stereochemical outcome of glycosylation with 2-O-TIPS substituted thioglucosides depends on acceptor nucleophility, as well as on the nature and anomeric configuration of aglycon. 

Acknowlegements

This work was supported by the Russian Science Foundation (Project No. 16-13-10244-P).

References: 
  1. Crich, D.; Sharma, I. J. Org. Chem. 2010, 75, 8383-8391.
  2. Baek, J. Y.; Kwon, H.-W.; Myung, S. J.; Park, J. J.; Kim, M. Y.; Rathwell, D. C. K.; Jeon, H. B.; Seeberger, P. H.; Kim, K. S. Tetrahedron 2015, 71, 5315-5320.
  3. Abronina, P. I.; Fedina, K. G.; Podvalnyy, N. M.; Zinin, A. I.; Chizhov, A. O.; Kondakov, N. N.; Torgov, V. I.; Kononov, L. O. Carbohydr. Res. 2014, 396, 25-36.
  4. Abronina, P. I.; Zinin, A. I.; Malysheva, N. N.; Stepanova, E. V.; Chizhov, A. O.; Torgov, V. I.; Kononov, L. O. Synlett 2017, 28, 1608-1613.
  5. Abronina, P. I.; Zinin, A. I.; Romashin, D. A.; Malysheva, N. N.; Chizhov, A. O.; Kononov, L. O. Synlett 2015, 26, 2267-2271.
  6. Abronina, P. I.; Zinin, A. I.; Romashin, D. A.; Tereshina, V. V.; Chizhov, A. O.; Kononov, L. O. Carbohydr. Res. 2018, 464, 28-43. 

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