A variety of cyclopentane scaffolds have been recently introduced to the Acros Organics product range via a recent collaboration with ChiroTech. Some examples of these products and the versatility of their chemistry are described below.

The parent compounds, azabicycloheptenones, 29704, 29705, are prepared by a bioresolution process that has been developed to run on multi tonne scale.ⁱ These products have been used as a starting material for the production of various carbocyclic nucleosides,ⁱⁱ and in the synthesis of the neuramidase inhibitor shown below.ⁱⁱⁱ In some cases the amino acid or a protected derivative can be used as well.

Through the introduction of two further hydroxyl groups,^iv derivatives such as products 36220, 36221 and 36223, are prepared and have seen utility in the synthesis of carbocyclic nucleosides as illustrated below.^v

Stereoisomers 36229-36236 (listed below) have also been prepared by further exploiting the rigidity and low molecular weight of the cyclopentane ring, coupled with the incorporation of three different functional groups to allow them to be used as the core molecule for the generation of a screening library.

The importance of stereochemistry is increasingly being recognised as key to the development of effective lead candidates and the provision of all the stereoisomers allows the relationship between the stereochemistry and the activity to be explored.^vi

References:

i. R. McCague et al, Tetrahedron: Asymmetry, 1993, 4,1117
ii. S.M. Roberts et al, J. Chem. Soc. Perkin Trans. 1, 1992, 589
iii. Y.S.Babu et al, J. Med. Chem., 2000, 43, 3482
iv. G.R. Ruecroft et al, Org. Proc. Res. & Dev., 1997, 1, 415
v. R. Kuang et al, Tetrahedron Lett., 2000, 41, 9575
vi. (a) R. McCague, Modern Drug Discovery, July 2000, 29 and
(b) M.E.B. Smith et al, Tetrahedron Asymm., 2001, 12, 703

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