Peter G. Griffiths

Quantitative studies on free radical reactions with the scavenger 1,1,3,3-tetramethylisoindolinyl-2-oxy

Abstract Previously unobserved reaction pathways for the attack of tert -butoxy radicals on vinyl monomers have been found by a technique which employs the title nitroxide as radical scavenging agent.

Detection of brassinosteroids in pollen of Lolium perenne L. by immunocytochemistry

Bioactive brassinosteroids have been localized in developing and mature pollen of anhydrously fixed rye-grass (Lolium perenne) by immunocytochemistry using polyclonal antibodies to castasterone generated in rabbits. Tricellular pollen fixed by freeze-substitution was also labelled in the starch granules. Study of the developmental sequence of the pollen through the microsporocyte, microspore, bicellular and tricellular stages showed that the brassinosteroids were increasingly sequestered in starch granules as the amyloplasts matured, supporting the view that these are storage organelles for these potent plant growth promoters. In bicellular pollen, heavy labelling was seen in the zone within 0.5 μm of the starch granule, where stromal tissue remains. Thus, the stroma may be the site of synthesis of these compounds. During aqueous fixation, the brassinosteroids leached from the starch granules of tricellular pollen, indicating that they would be quickly available after imbibition to influence the physiology of germinating pollen. The results from high-performance liquid chromatography of dansylaminophenylboronates from partially purified extracts of freshly dehisced tricellular pollen of rye-grass showed 25-methylcastasterone may be a minor component, together with two unknown peaks. No specific binding of brassinolide to any soluble proteins extracted from tricellular rye-grass pollen was observed using the antibodies in gel electrophoresis or enzyme-linked immunosorbent assays.

1,4-anthraquinonoid dienophiles applicable to synthesis of linear tetracycles

Abstract Derivatives of 1,4-anthraquinones (3), (21) are shown to be good dienophiles for achieving strongly regiocontrolled synthesis of linear tetracycles, a property greatly enhanced by their ease of formation and of subsequent replacement of the chloride.

Brassinolide-induced elongation

The promotive effects of brassinosteroids (BRs) on elongation seem general, as members of the family affect young vegetative tissue in fifteen species (listed in Sasse, 1991a). There is also a specific effect, as 24-epibrassinolide (24epiBL) forms part of the sequential response in young elongating tissue (Sasse, 1985). The case for BRs as a new family of plant hormones is strong (Sasse, 1991a); however, if BRs and their interactions with other natural plant growth regulators have an endogenous role in the control of plant growth, the compounds must be shown to occur in adequate amounts in appropriate tissuein vivo.

An expeditious synthesis of anthracyclines

Abstract Regiospecific cycloaddition of 2-oxybutadienes to derivatives of the 1,4-anthraquinone (6) efficiently leads to the tetracyclic ketones (4) and (5), which previously have been converted into daunomycin, adriamycin and related anticancer agents.

5-deoxyanthracyclines: New analogues of daunomycin and adriamycin

Abstract Hydrogenation of daunomycin(1) and adriamycin(2) has afforded deoxygenation at position 5 with retention of the 7-glycoside. The resulting 5-deoxyanthracyclines (3), (4), (12), (13) represent a new family possessing high anticancer activity.

5-Deoxy, 12-Deoxy, 5,12-Bisdeoxy, and 4,5,12-Trisdeoxy Anthracyclines: Synthesis of New Analogues of Daunorubicin and Doxorubicin by Controlled Deoxygenation of the C-Ring.

Hydrogenation of the anthracyclines daunorubicin (1) and doxorubicin (2) gave selective deoxygenation at position 5. Hydride reduction of (1) and (2) gave complementary regiocontrol, leading to 12-deoxygenation or 5,12- bisdeoxygenation. This chemistry allows retention of the 7-glycoside and the side-chain carbonyl groups. It has led to new anthracycline families possessing all of the stereochemical and most of the spatial characteristics of the parent compounds (1) and (2). These are typified by 5-deoxy (12), (15); 12-deoxy (22), (23); 5,12-bisdeoxy (34), (35); and 4,5,12-trisdeoxy systems (36). All possess high anticancer activity.

A new synthesis of anthracyclines

Abstract Carminomycinone (1) has efficiently been synthesised in a five-stage sequence based on cycloaddition of a 1,3-dioxybutadiene to the 1,4-anthraquinone (3); (1) was then converted into daunomycinone (2), an established source of daunomycin, adriamycin and related antiturmour anthracyclines.

Alkylation of 1,4,5-trihydroxyanthraquinone involving nitroalkanes. Syntheses of digitopurpone and (+/−)-10-deoxy-γ-rhodomycinone

Abstract C -Alkylation of 1,4,5-trihydroxyanthraquinone with nitroalkanes in alkali gives regioselective 3-substitution contrary to literature; this is applied to a two-step synthesis of the anthracyclinone 9 .

12-deoxy-, 5,12-bisdeoxy-, and 4,5,12-trisdeoxy-anthracyclines : new analogues related to daunorubicin and doxorubicin

Abstract Reduction of daunorubicin (1), doxorubicin (2), idarubicin (3) and carminomycin (6) has led selectively to 12-deoxygenation or 5,12-bisdeoxygenation of the aromatic nucleus, with retention of both side-chain carbonyl and glycosidic groups.