Carboxy Function Research Articles

Conversion of some monocyclic β-lactams into novel di-β-lactams

Monocyclic β-lactams (V & XI) carrying a carboxy function have been used to annelate the Schiff bases (II & X) using POCl 3 in the presence of triethylamine to obtain the di-β-lactams (VI & XII). Alternately, (VI) could also be prepared by annelation of the Schiff base (IX) derived from the α-amino-β-lactam (VIII), with phenoxyacetyl chloride.

Structure and enzymic activity of ribonuclease-A esterified at glutamic acid-49 and aspartic acid-53.

The dimethyl ester of bovine pancreatic ribonuclease-A (dimethyl RNAase-A), the initial product of esterification of RNAase-A in anhydrous methanolic HCl, was isolated in a homogeneous form. The two carboxy functions esterified in this derivative are those of glutamic acid-49 and aspartic acid-53. There were no changes in the u.v.-absorption spectral characteristics, the accessibility of the methionine residues, the resistance of the protein to proteolysis by trypsin and the antigenic behaviour of RNAase-A as a result of the esterification of these two carboxy groups. Dimethyl RNAase-A exhibited only 65% of the specific activity of RNAase-A, but still had the same K(m) value for both RNA and 2':3'-cyclic CMP. However, the V(max.) was decreased by about 35%. On careful hydrolysis of the methyl ester groups at pH9.5, dimethyl RNAase-A was converted back into RNAase-A. Limited proteolysis of dimethyl RNAase-A by subtilisin resulted in the formation of an active RNAase-S-type derivative, namely dimethyl RNAase-S, which was chromatographically distinct from dimethyl RNAase-A and had very nearly the same enzymic activity as dimethyl RNAase-A. Fractionation of dimethyl RNAase-S by trichloroacetic acid yielded dimethyl RNAase-S-protein and dimethyl RNAase-S-peptide, both of which were inactive by themselves but regenerated dimethyl RNAase-S when mixed together. Dimethyl RNAase-A-peptide was identical with RNAase-S-peptide. RNAase-S-protein could be generated from dimethyl RNAase-S-protein by careful hydrolysis of the methyl ester groups at pH9.5. The interaction of dimethyl RNAase-S-protein with RNAase-S-peptide appears to be about 4-fold weaker than that between the RNAase-S-protein and RNAase-S-peptide. Conceivably, the binding of the S-peptide ;tail' of dimethyl RNAase-A with the remainder of the molecule is similarly weaker than that in RNAase-A, and this brings about subtle changes in the geometrical orientation of the active-site amino acid residues of these modified methyl ester derivatives. It is suggested that these changes could be responsible for the generation of the catalytically less-efficient RNAase-A and RNAase-S molecules (dimethyl RNAase-A and dimethyl RNAase-S respectively).

ChemInform Abstract: IMPROVED DELIVERY THROUGH BIOLOGICAL MEMBRANES. 4. PRODRUGS OF L‐DOPA

AbstractNach bekannten Verfahren werden die Verbindungen (II) und (III) hergestellt, die als Vorstufen des L‐Dopa (I) angesehen werden können.

ChemInform Abstract: THE SYNTHESIS OF CUBEBOL FROM (‐)‐CARVONE BY INTRODUCING THE ELECTROCHEMICAL ACETOXYLATION REACTION

AbstractDer aus (‐)‐Carvon (I) erhältliche Halbester (IIa) wird in das Diazoketon (IIb) übergeführt, das durch thermische Zersetzung (in Gegenwart von Bis‐(N‐propylsalicylidenaminato)‐kupfer(II) als Katalysator) ein trennbares Gemisch der isomeren Addukte (IIIa) und (IIIb) liefert.

The Synthesis of Cubebol from (−)-Carvone by Introducing the Electrochemical Acetoxylation Reaction

Abstract The synthesis of cubebol and the related compounds from (−)-carvone is described. In the preparation of the key intermediate, 7,10-trans-2,6-epi-2-acetoxy-7-isopropyl-10-methyltricyclo[4.4.0.01,5]decan-4-one (10) the electrochemical acetoxylation reaction could be used as an effective method for introducing the acetoxy group at C-2 carbon atom instead of the carboxy function of 7,10-trans-2,6-epi-4-oxo-7-isopropenyl-10-methyltricyclo-[4.4.0.01,5]decan-2-carboxylic acid (6a). The condensation of (+)-p-menth-8-en-2-one (2a) prepared from (−)-carvone with dimethyl succinate afforded Stobbe half-ester 3, which provided the diazoketone 4 smoothly. Thermal decomposition of 4 in benzene gave intramolecular adducts 5a and 5b (4 : 1). Hydrolysis of 5a afforded 6a in ca. 40% yield. Electrolysis of 6a in AcOH-t-BuOH-Et3N (2 : 1 : 0.1) using platinum electrodes gave 10 in 72% yield. Elimination of acetic acid gave two isomers 11a and 11b (3 : 1) in 87% yield and subsequent methylation of 11a afforded 7-isopropyl-4,10-dimethyltricyclo[4.4.0.01,5]deca-2-en-4-ol (12) in 82% yield, which on hydrogenation gave the desired product 1a (36.5%) along with the epimer 1b (36.5%).