To enzyme analogues by lock and key chemistry with crown compounds. Part 1. Enantiomeric differentiation by configurationally chiral cryptands synthesised from L-tartaric acid and D-mannitol

Abstract

The requirements of an enzyme analogue are discussed in terms of (i) binding, (ii) chirality, and (iii) functionality. The ability of 18-crown-6 derivatives to complex with primary alkylammonium cations indicates the potential of the 18-crown-6 constitution to provide the binding requirement of an enzyme analogue. Attention is drawn to the fact that carbohydrates provide not only functionality but also a relatively inexpensive source of chiral bismethylenedioxy units for incorporation into the 18-crown-6 framework. The optically pure configurationally chiral cryptands L-(14), LL-(15), LL-(16), LL-(17), DD-(17), LL-(18), DD-(28), D-(29), DDD-(30), DD-(31), DD-(32), and DD-(33) have been synthesised from L-tartaric acid and D-mannitol. The 18-crown-6 locks excluding the tetraol LL-(16) and the octaol DD-(31), have been shown by ¹H n.m.r. spectroscopy to form complexes in CD₂Cl₂ with primary alkylammonium salts. The stability constants for complexes formed in CDCl₃ solution between (i) t-butylammonium thiocyanate and (ii) benzylammonium thiocyanate and some of these 18-crown-6 locks have been determined by an ¹H n.m.r. spectroscopic method and compared with the complexing ability of 18-crown-6 (34). ¹H and ¹³C N.m.r. spectroscopy has been used to demonstrate that the locks LL-(18) and DD-(28) exhibit enantiomeric differentiation in complexation equilibria towards (RS)-α-phenylethylammonium hexafluorophosphate [(RS)-(8),HPF₆]. The tetraol LL-(16) and the octaol DD-(31) have been shown by ¹H n.m.r. spectroscopy to form complexes in CD₃OD and D₂O with primary alkylammonium salts. The tetra-O-isopropylidene derivative DD-(28) forms strong complexes in methanolic solution with alkali metal cations.