A novel non-pyrogenic carbocyclic muramyl dipeptide (MDP) analogue, N-¿trans-2-[[2'-(acetylamino)cyclohexyl]oxy]acetyl¿-L-alanyl-D-glutamic acid, was obtained by replacement of the N-acetylmuramic acid part and the D-isoglutamine residue of the MDP molecule by a trans-2-[[2'-(acetylamino)cyclohexyl]oxy]acetyl moiety and D-glutamic acid, respectively. The title compound was selected as a promising candidate for further evaluation among several related analogues on the basis of an immunorestoration test in mice. This novel nor-MDP analogue protects mice against the immunosuppressive effect of cyclophosphamide and increases the nonspecific resistance of mice against fungal infection. It is an immunomodulator which enhances the maturation of lymphocytes B to plasma cells and increases the activity of lymphocytes B and lymphocytes T as well as that of macrophages but does not alter the number of these cells.

Attempts to induce enantioselectivity in the catalytic hydrogenation of unsymmetrically substituted aromatics using covalently bound, well known chiral auxiliaries are described. Marked differences in stereoselectivity and rate of hydrogenolysis are noted as a function of the auxihary used. Enantioselectivities obtained in the resulting cyclohexyl derivatives are rather poor. o 1995 Wiey-Liss, hc.KEY WORDS: prochirality, rhodium, chn-a1 auxiliaries, (-)-menthol, L-prohe, chiral cyclohexane derivativesHighly substituted chiral cyclohexyl moieties frequently constitute essential parts of biologically very active compounds like FK 506 (a potent immunosuppressor, Fig. 1)'"~~ and rapamycin (an antifungal agent) and in the synthesis of trichotecenes2 and GABA antagonist^.^The classical ways to such fragments are asymmetric Diels-Alder reactions4 or strategies applying the "chiral pool" concept,' some using enzymatic methods. We succeeded in using the most simple approach (Fig. 2): hydrogenation of appropriately substituted aromatic compounds (e. g., vanillic acid)7 and enzymatic resolution of the enantiomers with the help of enzymes8 shortens the preparation from 10 (the average of the reported syntheses) to 4 steps.From a theoretical point of view, unsymmetrically substituted aromatics can be regarded as prochiral entities (Fig. 3). Hansong in his original paper regarding prochirality, although not explicitly mentioning aromatics, implicitly included them: "It may be desirable in the future to define. . . planar prochirality. . . . It remains to be determined which combination of symmetry elements, i.e. which point groups, are compatible with prochxality. " If one is able to exploit this property, enantioselective hydrogenations of appropriately substituted benzene rings should be possible.In principle, four ways to such selective transformations can be envisaged: Here we report on our attempts regarding the second route. MATERIALS AND METHODSMelting points were determined with a Buchi apparatus and are uncorrected. Optical rotations were measured w i t h a 0 1995 Wiley-Liss, Inc.JASCO DIP-370 polarimeter. NMR spectra were recorded on a Varian Gemini instrument (199.98 MHz for 'H and 50.29 MHz for 13C). Chemical shifts are in ppm relative to TMS as internal standard. For the analysis of the product mixture of the hydrogenation of 6a GLC was used DAN1 8500, column DB-1701, 1 = 30 cm. No internal standard was used. Reactions were monitored by TLC using Merck silica gel 60 F, , plates. Purification of the products was performed on Merck silica gel 60. All reagents and solvents were obtained from commercial suppliers and used without further purification.The Rh catalysts were donated by Johnson Matthep. '' Hydrog e n a t i o n~~~ were done in a Berghoff autoclave, 250 ml, m a . 150 bar. 4-Acetoxy-3-methoxybenzoic Acid (2)Vanillic acid, 10.0 g (59.4 mmol), was dissolved in 100 ml CH,CI, and 12.0 ml (148.7 mmol) pyridine and 8.4 ml (89.2 mmol) acetic anhydride added. The mixture was heated under reflux for 3 days....

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