Synthesis of 4-Membered Carbasugars by Way of Stereoselective SmI₂-Mediated Aldehyde–Alkene Cyclization

Abstract

A stereodivergent synthesis of the first examples of 4-membered carbasugars has been achieved from vitamin C by way of an efficient intramolecular SmI2-mediated aldehyde-alkene coupling. In this key step, cylobutanes with four contiguous asymmetric centers are generated with a high level of stereocontrol.

Carbohydrates to Cyclitols Using Mn/CrCl3‐Mediated Domino Bernet‐Vasella Reductive Elimination and NHK Reaction

“…After studying our strategy on furanose and pyranose derivatives, we turned our attention to its applicability for preparing the chiral tetrasubstituted cyclobutanes, which are generally difficult to synthesize ,. For the synthesis of 4‐membered carbasugars, we need to have diiodo compound VII .…”

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 After studying our strategy on furanose and pyranose derivatives, we turned our attention to its applicability for preparing the chiral tetrasubstituted cyclobutanes, which are generally difficult to synthesize. [7,20] For the synthesis of 4membered carbasugars, we need to have diiodo compound VII. For this, compound 28, [21] on iodination using imidazole, TPP and iodine afforded the diiodo compound 29.…”

“…For example, cyclobut‐A 10 inhibits the infectivity of HIV in T cells and suppressed the replication of a monocytotropic strain of HIV‐1 in monocytes and macrophages. Recently, synthesis of chiral hydroxy cyclobutane derivatives 11 and 12 were reported by Compain et al …”

Synthesis and Therapeutic Applications of Iminosugars in Cystic Fibrosis

“…In this case, the rigid bicyclic system was conceived with the idea to reproduce the structure of bioactive iminosugars (e.g., DNJ and castanospermine), while more closely resembling the conformation of the substrates of carbohydrate-processing enzymes in their transition states [148,149]. The synthesis of 68-70 relied on the Rh(II)-catalyzed C(sp 3 )-H amination of carbamate 65 (in turn obtained from vitamin C [150]) enabling a stereoselective C-N bond formation in 66 [151,152]. Subsequent N-allyl carbamate formation followed by ring-closing metathesis using Grubbs II catalyst provided intermediate 67.…”

Spiro Iminosugars: Structural Diversity and Synthetic Strategies

“…However, applying such a reaction to polyoxygenated substrates represents a challenge in terms of regioselectivity since insertion is known to be favoured in α-ethereal C-H bonds. The first part of the synthesis is the preparation of the functionalized square carbasugar 16 [24,25]. This key intermediate was obtained in 67% yield by way of SmI 2 -mediated intramolecular coupling reaction of γ,δ-unsaturated aldehyde 15 prepared in 6 steps from vitamin C [24].…”