R. Ramage

Peptides—XXXII: The use of phenyl esters in peptide synthesis

Abstract Phenyl esters of N-terminal amino-protected peptides are valuable intermediates in synthesis of polypeptides. The phenyl ester function is stable during the customary manipulations of chain extension, and it can be removed selectively by treatment with one equivalent of hydrogen peroxide at pH 10.5 in a variety of solvents such as 80% acetone, dimethylfonnamide, hexamethylphosphoramide or trifluoroethanol. The method has always been satisfactory providing that dimethylsulphide is used as a scavenger.

A NEW SYNTHETIC ROUTE TO (±) LYSERGIC ACID

Abstract A route to the synthesis of lysergic acid, 1 is described based on a mechanism proposed for the racemisation of lysergic acid and related compounds. The strategy involves cyclisation of the aminodienoic esters 19 and 22 to produce tetrahydropyridine systems. A modified Curtius degradation sequence is described.

A stereospecific total synthesis of zizanoic and isozizanoic acids

Abstract The total syntheses of zizanoic and isozizanoic acids, 5a and 37a respectively have been achieved starting from D (+)-camphor and utilising rearrangement of a tricyclo [6.2.1.0 1,6 ] undecane system to form the desired tricycle [6.2.1.0 1,5 ] undecane skeleton of the tricyclovetivane class of sesquiterpenes. An intermediate ( 33 ) has also been synthesised which can be transformed into epizizanoic acid ( 36a ).

The structure and synthesis of speciosine

Abstract The structure of speciosine ( 1 ) was deduced by spectroscopic methods and confirmed by synthesis from demecolcine ( 2 ) and 2-bromomethylphenyl acetate ( 6 ).

Gel filtration of protected peptides on Sephadex G-50 in hexamethylphosphoramide containing 5% water

Gel permeation chromatography on G-50 and G-75 Sephadex gels, using 5% water in hexamethylphosphoramide (phosphoric trisdimethylamide) has been applied to the purification of large protected peptides which are outside the molecular weight range of the Sephadex LH-20-dimethylformamide system.

Peptides—XXXII: Synthesis of a polypeptide chain comprising 129 residues. Strategy and tactics☆

Abstract A plan for synthesis of a small protein by fragment condensation with side-chain protection by t-butyl, adamantyloxycarbonyl and acetamidomethyl groups is discussed.

Peptides—XXXVI: Synthesis of the 27–37 fragment of a lysozyme analogue

Abstract Combination of the protected peptide fragments 1–16, 17–26 and 27–37 to yield the 1–37 portion of a lysozyme analogue is described. The fragments were combined using DCCI with the addition of HONSu, and the products purified mainly by gel filtration.

THE ACTIVATION OF N‐HYDROXY COMPOUNDS BY μ‐OXO‐BIS(TRIS(DIMETHYLAMINO)PHOSPHONIUM)‐BIS‐TETRAFLUOROBORATE

Abstract A study is made of the effect of 1-hydroxybenzotriazole on μ-oxo-bis-[tris(dimethylamino)-phosphonium]-bis-tetrafluoroborate 1 during amide bond formation. The reagent 1 is used to activate phenylhydroxamic acid towards a Lossen-type rearrangement and bring about Beckmann rearrangement of ketoximes under mild conditions. Both syn - and anti -benzaldoxime give benzonitrile by elimination.

Peptides-XXXXV: Synthesis of the 118–129 fragment of a lysozyme analogue

Abstract The synthesis of the (118–129) fragment of a Lysozyme analogue was achieved by the fragment coupling approach. The fragments were assembled using the DCCI/HONSu method and the (118–122), (123–126) and (127–129) subfragments were each built up in a stepwise manner. At several stages the diphenylphosphinic mixed anhydride method was found to be superior to the pivalic mixed anhydride method.

Peptides-XXXXVI: Studies in the synthesis of an analogue of hen egg white lysozyme

Abstract The previously synthesised (1–37), (38–75), (76–93), (94–104), (105–117) and (118–129) fragments of the analogue were combined making extensive use of the DCCI/HONSu method. The final coupling involved the (1–75) and (76–129) sub-fragments. Aggregation of the latter fragment caused problems in purification by routine gel filtration methods employing Enzacryl K2 or Sephadex LH60. The fully protected (1–129) product was partially purified by washing, then deprotectcd and purified by gel filtration and ion exchange chromatography. Satisfactory removal of the acetamidomethyl group used for cysteine protection could not be achieved.