Graham R. Geen

The effect of the c-6 substituent on the regioselectivity of n-alkylation of 2-aminopurines

Abstract A series of eleven 6-substituted 2-aminopurines was N-alkylated with 2-acetoxymethyl-4-iodobutyl acetate. The ratio of N-9 to N-7 alkylated products varied from 1.8:1 (6-methoxy) to 25:1 (6-isopropyl). The log of this ratio was found to correlate with a combination of resonance and lipophilicity parameters of the C-6 subsdtuent of the purine.

Regiospecific Michael additions with 2-aminopurines

Abstract N-9 alkylated materials are the sole products obtained from extended reaction of 2-aminopurines (potential guanine precursors) with Michael acceptors. This was used as the basis for a highly regioselective synthesis of famciclovir, the oral form of the anti-herpesvirus agent penciclovir.

The effect of catalyst loading and donor ligands in the Mn(III) salen catalysed chiral epoxidation of chromenes: Synthesis of BRL 55834

Abstract In the absence of a donor ligand both the reaction rate and product e.e. of the manganese (III) salen catalysed epoxidation of 2,2-dimethyl-6-pentafluoroethylchromene were dependent on the catalyst loading. Isoquinoline N-oxide was the most effective donor ligand, affording highly efficient epoxidations with catalyst loadings of 0.1–0.4 mol%. These findings allowed the realisation of a concise, inexpensive synthesis of BRL 55834.

A Direct Approach to the Synthesis of Famciclovir and Penciclovir

Abstract Reaction of 2-amino-6-chloropurine with triethyl 3-bromopropane-1,1,1-tricarboxylate followed by decarbethoxylation/transesterification of the unpurified product was the key sequence in synthesising both the anti-herpesvirus agent penciclovir and its oral from famciclovir in three isolated steps.

Regioselective alkylation of guanines using 2-acetoxytetrahydrofurans

Abstract Reaction of silylated guanine derivatives with 2-acetoxy-4-benzoyloxymethyltetrahydrofuran in DMF or NMP resulted in selective N-9 alkylation. This was used as the basis for a regioselective synthesis of the anti-viral agents famciclovir and penciclovir.

Influence of Remote Structure Upon Regioselectivity in the N-Alkylation of 2-Amino-6-Chloropurine: Application to the Synthesis of Penciclovir

Abstract Reaction of 2-amino-6-chloropurine with trans-2-alkyl-5-iodoethyl-1,3-dioxanes under basic conditions afforded N-9 and N-7 alkylated products, the product ratio obtained being dependent on the size of the 2-alkyl group. This allowed a highly regioselective key step in the synthesis of the anti-herpes agent penciclovir.

Stereoselectivity in the Peterson reaction - application to the synthesis of BRL 49467.

Abstract The E:Z selectivity in the introduction of the tri-substituted double bond in BRL 49467 could be controlled by the choice of base and silyl group used in a Peterson olefination reaction. The method allowing optimum E-selectivity was developed such that it could be scaled up to 100mmol.

A versatile synthesis of benzo[c]phenanthridine alkaloids

Suzuki coupling between 2-bromo-1-formamidonaphthalenes and arylboronic acids is the key step in a versatile synthesis of benzo[c]phenanthridine alkaloids, illustrated by the synthesis of norallonitidine, nornitidine, noravicine, allonitidine, nitidine and avicine.