A unique category of basic side chain containing amino acid derived sulfonyl fluorides (SFs) has been synthesized for incorporation into new proteasome inhibitors targeting the trypsin-like site of the 20S proteasome. Masking the former α-amino functionality of the amino acid starting derivatives as an azido functionality allowed an elegant conversion to the corresponding amino acid derived sulfonyl fluorides. The inclusion of different SFs at the P site of a proteasome inhibitor resulted in 14 different peptidosulfonyl fluorides (PSFs) having a high potency and an excellent selectivity for the proteolytic activity of the β2 subunit over that of the β5 subunit. The results of this study strongly indicate that a free N-terminus of PSFs inhibitors is crucial for high selectivity toward the trypsin-like site of the 20S proteasome. Nevertheless, all compounds are slightly more selective for inhibition of the constitutive over the immunoproteasome.

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COMMUNICATIONS filtered and cirr-drieci 10 yield 2-2 PF, (232 mg. 95 %)as a yellow powder: m.p. 282 C (dscomp.). FAB-MS 171;: 531 ( M -PF,)'. 386 ( M -2PF,)': ' H NMR (CD,CN). d = 6.75 (4H. s). 7.51 ~ 7.55 (6H. m). 7.62-7.67 (4H. m). 8.81 (4H. s).

A facile synthesis of 4,6-dideoxy-3-O-methyl-D-xylo-hexose (D-chalcose) is described, which involves the preparation of methyl 4,6-dichloro-4,6-dideoxy-3-O-methyl-D-galactopyranoside (2) by a reaction with sulfuryl chloride, and its reduction to the dideoxy sugar by hydrogenation over Raney nickel.

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An analogue of LHRH containing an extension of Gly‐Cys at the carboxyl‐terminus has been designed to permit reproducible coupling to a suitably modified carrier via a thioether bond. Potential energy calculations indicated that this analogue adopted a conformation in solution virtually identical to the type II′ turn around Gly‐6—Leu‐7 predicted for native LHRH. Intradermal administration of a conjugate of this analogue with purified protein derivative of tuberculin to male rats previously primed with BCG vaccine rapidly led to complete testicular regression. This adjuvant‐free immunisation protocol may represent an alternative to castration for the veterinary control of reproductive function.

NG7 2RD) Summary 2H N.m.r. spectroscopy has been employed to (1) and -isoflavanone (3) are excellent biosynthetic preestablish that in fenugreek seedlings, (gal?, 1laR)-de-cursors of the pterocarpan phytoalexin (6a22,llaR)methylhomopterocarpin is synthesised from 2', 7-di-demethylhomopterocarpin (4) in CuC12-treated seedings of hydroxy-4'-methoxyisoflavone via an overall trans red clover (Trifolium pratense) and lucerne (Medicago addition of hydrogen to the double bond. sativa). The biosynthetic pathway to (4) most probably proceeds via reduction of (1) to (3), further reduction to the isoflavanol (6), then cyclisation to the pterocarpan. An intermediate carbonium ion (7), or its mesomeric counter-FEEDING experiments132 using 14C-labelled compounds have demonstrated that 2',7-dihydroxy-4'-methoxy-isoflavone part, has been postulated.2 L. Crombie, Chemistry Department, for n.m.r. facilities.

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