Alf Claesson

A 2-deoxy analogue of KDO as the first inhibitor of the enzyme CMP-KDO synthetase.

The two KDO analogues 2,6-anhydro-3-deoxy-D-glycero-D-galacto-octonate and 2,6-anhydro-3-deoxy-D-glycero-D-talo-octonate were synthesized and tested as inhibitors of the enzyme CTP:CMP-deoxyoctulosonate cytidylyltransferase (CMP-KDO synthetase) from Gram-negative bacteria. Only compound 4, the 2-deoxy analogue of beta-KDO-pyranose, was found to be an inhibitor with a Ki of 3.9 microM.

Synthesis of conjugated dienes by nickel-catalyzed reactions of 1,3-alkadien-2-yl phosphates with grignard reagents

Abstract 2-Substituted 1,3-alkadienes were prepared in good yields by reactions of diethyl 1-methylene-2-propenyl phosphate and diethyl 1-methylene-3-phenyl-2-propenyl phosphate with various Grignard reagents in the presence of nickel(II) catalysts.

Synthesis of analogues of 3-deoxy-D-manno-octulosonic acid (KDO) as potential inhibitors of CMP-KDO synthetase

A series of derivatives of the 2-deoxy analogue of beta-KDO (2,6-anhydro-3-deoxy-D-glycero-D-talo-octonic acid; ammonium salt, 2) has been synthesised as potential inhibitors of CMP-KDO synthetase, starting from methyl 2,6-anhydro-3-deoxy-4,5:7,8-di-O-isopropylidene-D-glycero-D-talo- octonate and replacing the CO2Me group attached to C-2 variously by CONH2, CONHOH, CH2OH, CH2PO(OH)(O-NH4+), COCH2PO(OH)(O-H3N+pheny), CH2CO2-NH4+, CON-HCH2CO2-NH4+, CONHBn, CONHHexyl, CO2Bn, and CO2Hexyl. Of these derivatives, the hydroxamic acid (CONHOH) was the best inhibitor of CMP-KDO synthetase, but was less potent than 2.

Allenes and acetylenes XXVI. Organocuprate reactions of 1,3-alkadien-2-yl phosphates. a new approach to the synthesis of allenes

Abstract Allenic hydrocarbons and one γ-allenic ketone were prepared in poor to good yields by the reactions of diethyl 1-methylene-2-propenyl phosphate and diethyl 1-(1-cyclohexenyl) phosphate with various organocuprates.

Mechanistic aspects of reductions of allylic ethers and acetates with organocuprates

Abstract The rate of substitution to reduction has been investigated for reactions of three phenyl-substituted allylic ethers and the corresponding acetates with EtMgBr plus 10 or 25% copper(I) bromide in THF. It is found that the relative amount of reduction increases with increased electron delocalization in the postulated copper(III)-bound allyl ligand, and is also dependent on the nature of the leaving group; methoxy giving much more reduction product than acetoxy. Furthermore, for one acetate investigated there was more reduction at −65° than at −25°C. The results are interpreted in terms of relative binding strength of allyl ligands to a copper(III) intermediate.

Structural analysis of two 2-deoxy analogues of α- and β-KDO and the methyl α- and β-glycosides of KDO, and determination of their metal-ion-binding properties

Abstract Ammonium 2,6-anhydro-3-deoy- d - glycero - d - talo -octonate ( 1 ), a potent inhibitor of the enzyme CMP-KDO synthetase, its C-2 epimer 2 , and the methyl β-( 3 ) and α-glycoside ( 4 ) of KDO were studied by 1 H- and 13 C-n.m.r. spectroscopy. Compound 1 was also analysed by X-ray crystallography. Each compound adopted a 5 C 2 chair conformation with the side chain equatorial. The preponderant side-chain conformation of 1 in solution was the same as that in the crystal and was stabilised by an intramolecular hydrogen bond from HO-8 to the carboxylate group. This hydrogen bond appeared to be present also in 3 . However, the side-chain conformation of 2 and 4 was different from that in 1 and 3 . The metal-ion-binding properties, determined on the basis of the line-broadening effects of Mn 2+ on the 13 C-n.m.r. signals, showed that the carboxylate group was involved in the binding with O-8 in 1 and 3 and with O-6 and O-8 in 2 and 4 .

Stereochemistry of the organocuprate reactions of two cis–trans isomeric allylic ethers

(S)-cis-4-(1-Ethoxyethoxy)pent-2-en-1-ol reacts with methylmagnesium iodide in the presence of CuI to give (S)-2-methylpent-3-en-1-ol in an overall trans substitution, whereas (S)-trans-4-(1-ethoxyethoxy)pent-2-en-1-ol gives rise to the (R)-enantiomer, also in a trans substitution.

Allenes and acetylenes XVII. Allenic amines from organocuprate reactions

Aus den Acetylen-aminen (I) entstehen mit Butylmagnesiumbromid in Gegenwart von CuJ die Allenyl-Verbindungen (II), die zu Allen-aminen (III) hydrolysiert werden.

Chiral allenes are racemised by organocuprates

The chiral allenes (1) and (2) are racemised in the presence of various organocuprates, or, in the case of the alcohol (2), by methylmagnesium iodide alone; the racemisations probably proceed via an anion radical.