Gordon L. Hodgson

Biosynthesis of porphyrins and related macrocycles. Part III. Rational syntheses of [β-13C]-, [γ-13C]-, and [δ-13C]-protoporphyrin-IX: assignment of the 13C nuclear magnetic resonance signals from the meso-carbon atoms of protoporphyrin-IX dimethyl ester

The 13C signals arising from the meso-carbon atoms ot protoporphyrin-IX are of key importance for biosynthetic studies. Rigorous assignment is made of the signals from the β- and δ-carbon atoms by synthesis of [β-13C]- and [δ-13C]-protoporphyrin-IX dimethyl ester from unsymmetrical pyrromethenes in 42% yield. The formation of porphyrins from a,c-biladienes and formaldehyde is studied and leads to synthesis of [γ-13C]protoporphyrin-IX dimethyl ester. The spectrum of this product allows assignment of the two remaining signals, from the γ- and α-carbon atoms. The three 13C-labelled samples of protoporphyrin-IX dimethyl ester are converted into 2,4-diacetyldeuteroporphyrin-IX dimethyl ester; assignment is thereby made of the well-spread 13C signals from the meso-carbon atoms of this porphyrin. 13C Chemical shifts are reported for a variety of pyrrole derivatives and porphyrins.

Synthesis of (±)-campherenone, (±)-epicampherenone, (±)-β-santalene, (±)-epi-β-santalene, (±)-α-santalene, (±)-ylangocamphor, (±)-copacamphor, and (±)-sativene

The completion of part of a general synthetic route to sesquiterpene analogues of camphor, bornan-2-ol, camphene and tricyclene is illustrated by an alternative total synthesis of campherenone and epicampherenone [the epimeric 1,7-dimethyl-7-(4-methylpent-3-enyl)norbornan-2-ones], β-santalene and epi-β-santalene [2-methyl-3-methylene-2-(4-methylpent-3-enyl)norbornanes], α-santalene {1,7-dimethyl-7-(4-methylpent-3-enyl)tricyclo-[2.2.1.02,6]heptane}, and the perhydro-1,4-methanoindene derivatives copacamphor, ylangocamphor, and sativene.

A stereospecific synthetic route to campherenone, campherenol, epicampherenone, β-santalene, epi-β-santalene, ylangocamphor, copacamphor, sativene, and copacamphene

A simple and efficient synthetic route to either enantiomeric form of campherenone and epicampherenone [the epimeric 1,7-dimethyl-7-(4-methylpent-3-enyl)norbornan-2-ones], β-santalene and epi-β-santalene [2-methyl-3-methylene-2-(4-methylpent-3-enyl)norbornanes], and the perhydro-1,4-methanoindene derivatives copacamphor, copacamphene, ylagocamphor, and sativene is described. The simplicity of the synthetic route is due to the application of a general synthetic plan and the development of a new process for effecting direct 8-substitution of camphor.

Synthesis of (±)-camphor

An alternative proposal for the biosynthesis of the bornane series of bicyclic monoterpenes forms the basis of a new synthesis of camphor from p-menth-8-en-2-one (dihydrocarvone).

Synthesis and absolute configuration of the terpenes (–)-campherenone,(+)-epicampherenone, (–)-β-santalene, and (+)-epi-β-santalene

Biosynthetic considerations prompted synthetic studies which have resulted in reassignment of absolute configuration to (–)-campherenone and have established the absolute configuration of (+)-epicampherenone, (–)-β-santalene, and (+)-epi-β-santalene.

Biosynthesis of porphyrins and related macrocycles. Part VI. Nature of the rearrangement process leading to the natural type III porphyrins

Logical analysis of the problem posed by the constant formation in nature of type III porphyrins, e.g. protoporphyrin-IX (6), focuses attention on C–C bond making and bond breaking around the carbon atoms from which the interpyrrolic bridges are built (at C-5, C-10, C-15, and C-20). An approach to the study of such processes is outlined, based on double [13C] labelling combined with n.m.r. spectroscopy.[2,11-13C2]Porphobilinogen (17) has been prepared and applied (a) to determine the size of 13C–13C coupling for directly bonded carbon atoms in the porphyrin macrocycle and (b) to indicate that a biosynthetically significant 13C–13C coupling occurs between carbon atoms separated by three bonds. A coupled enzyme system has been developed from chicken blood cells and beef liver mitochondria which produces sufficient protoporphyrin-IX for spectroscopic and chemical work (20–30 mg); a similar system from Euglena gracilis is also described.[2,11-13C2] Porphobilinogen diluted with unlabelled porphobilinogen has been converted enzymically into protoporphyrin-IX; the 13C spectra of the dimethyl ester (i) as such, (ii) with a praseodymium shift reagent, and (iii) after chemical modification establish that the formation of type III porphyrins by both enzyme systems (avian and algal) is characterised by the same three precise features which are described.

Synthesis, absolute configuration, and photocyclisation of the sesquiterpene (–)-cryptomerion

The absolute configuration of cryptomerion has been established by synthesis from (–)-carvone and the conversion of cryptomerion into photocryptomerion is reported.