R.G. Kinsman

1,2-dihydroisoquinolines—VIII : Rearrangement—II☆

Abstract The acid promoted rearrangement of 1-allyl-2-methyl-1,2-dihydroisoquinoline to the corresponding 3-allyl-2-methyl-3,4-dihydroisoquinoline salt has been observed and the behaviour of 1-benzyl-2-methyl-1,2-dihydroisoquinoline and 2-methyl-1,2-dihydropapaverine towards various conditions of acid concentration and temperature has been studied.

1,2-dihydroisoquinolines—XV : Rearrangement III

Abstract The acid-catalysed rearrangement of a 1-allyl-1,2-dihydroisoquinoline into a 3-allyl-3,4-dihydroisoquinolinium salt has been shown to occur in an intra 1-propargyl-1,2-dihydroisoquinoline into a 3-allenyl-3,4-dihydroisoquinolinium salt is also described.

Direct cyanation of the furan nucleus by chlorosulphonyl isocyanate

Abstract A series of furans are converted directly,by reaction with chlorosulphonyl isocyanate, into furancarbonitriles. A route to furfuralcarbonitriles is described involving a new application of the ruthenium dioxide - sodium metaperiodate oxidizing system.

Structure-activity studies with fragments and analogues of salmonid melanin-concentrating hormone

A number of cyclic and linear fragments and analogues of MCH were synthesized and their biological potencies tested using the isolated carp scale melanophore assay. In this system the cyclic portion MCH(5-14) exhibited only 0.1% bioactivity, which was markedly enhanced by the addition of the exocyclic sequences MCH(15-17) and MCH(1-4). The exocyclic sequence itself, MCH(1-4,15-17), had minimal activity, however. Substitution of Tyr11 with phenylalanine reduced the potency of the ring structure MCH(5-14) by about 4-fold. Substitution of Gly8 with D-alanine reduced the potency of MCH(5-14) 16-fold, while both substitutions together caused a still more marked reduction (200-fold) in bioactivity. Linearized fragments of MCH, extending from MCH(15-17) to [Cys(Acm)5,14]MCH(1-17), showed a progressive increase in potency. The linearized forms of MCH, MCH(5-17) and MCH(5-14), were approximately 100-fold or less potent than their cyclic forms. The significant increases in bioactivity produced by the addition of the C- and N-terminal exocyclic sequence even to these linearized forms further emphasizes the importance of these regions for interaction at the receptor site.

Stereoselectivity in the synthesis of 2,5-disubstituted pyrrolidines

Under homogeneous conditions, the silver(I)-catalysed cyclisation of the allenic amine derivatices (3a–c), thogh not (3d), is stereoselective giving cis-2,5-disubstituted pyrrolidines in high yield; cyclisation on (3a), using a heterogeneous silver(I)-catalyst, is nonstereoselective.

Pavinane and isopavinane alkaloids: Correlation of absolute configurations by synthesis

Abstract (−)-Caryachine ( 9 ) and (−)-Reframoline ( 10 ) have been synthesised from a common intermediate; this confirms the absolute configuration in the isopavinane series deduced previously by application of the aromatic chirality rule. This also represents the first synthesis of an optically active pavinane alkaloid.

SPACER MOLECULES IN PEPTIDE SEQUENCES : INCORPORATION INTO ANALOGUES OF ATRIAL NATRIURETIC FACTOR

The spacer reagents FmocHN(CH2CH2CH2)3CH2COOPfp (1b) and FmocHN(CH2CH2O)3CH2COOPfp (2d) have been prepared and used to substitute for tetra-residue sequences in the cyclic portion of Atrial Natriuretic Factor (ANF) by solid phase peptide assembly.

Binding and biological activity of C-terminally modified melanocortin peptides: a comparison between their actions at rodent MC1 and MC3 receptors.

Five subtypes of melanocortin receptors have to date been identified, but to date little is known about the different structural requirements for binding and biological activity at these receptors. In this study, the role of C-terminal melanocortin peptide residues in imparting selectivity for the receptor subtypes was examined. C-terminally modified analogues of alpha-MSH and gamma-MSH were synthesized and their interaction with MC1 and MC3 melanocortin receptors was investigated. This study provides further evidence for an important role of proline 12 (numbering with respect to alpha-MSH) for binding and activity at the MC1 receptor. Although the influence of C-terminal amino acids on binding and activity at MC3-R was less marked, some of them were nevertheless observed to be beneficial for the interaction with this receptor subtype.

1,2-Dihydroisoquinolines—XX: Rearrangements—VI

Abstract A mechanism is proposed for the rearrangement of 1 - benzyl - 1,2 - dihydroisoquinolines into 3 - benzyl - 3,4 - dihydroisoquinolines involving a bimolecular exchange reaction. Two transition states are considered, and it is believed that both can be involved, depending upon the precise nature of the starting enamine.

1,2-dihydroisoquinolines—XVIII Rearrangements—IV: Dihydroisoquinoline rearrangement—15

Abstract When 1-allyl-2-methyl-1,2-dihydropapaverine is treated with hot, dilute mineral acid, rearrangement occurs to give, almost exclusively the 3-allyl-2-methyl-3,4-dihydropapaverinium salt. The previously reported rearrangement of 1-cinnamyl-2-methyl-6,7-dimethoxy-1,2-dihydroisoquinoline has been re-examined and the earlier result, that rearrangement occurs yield the 3-cinnamyl-3,4-dihydroisoquinolinium salt, confirmed.