Synthetic approaches towards Griseusin A

Kee, Alexander Andrew (1987) Synthetic approaches towards Griseusin A. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Synthetic studies towards a lactone precursor of the spiroacetal pyranonaphthoquinone Griseusin A are described. The basic approach involved the uncatalysed addition of 2-trimethylsiloxyfuran to 1,4-naphthoquinones. Reaction of 1,4-naphthoquinone with this siloxyfuran gave no useful products. Model studies showed that the addition of the siloxyfuran to various 2-carboxy-1,4-benzoquinones in acetonitrile followed by methanolic work-up afforded adducts with the cis 3a, 8b-dihydro-furo[3,2-b]benzofuran-2(3H)-one ring system in good yield. Reaction with naphthoquinones gave adducts with the corresponding cis 6b,9a-dihydro-furo[3,2,-b]naphtho[2,l-d]furan-8(9H)-one ring system. Treatment of cis 6b, 9a-dihydro-6-carbomethoxy-5-hydroxy-4-methoxy furo [3,2-b]naphtho [2,l-d]furan-8(9H)-one (168) with aqueous ceric ammonium nitrate afforded (4R), (5S)4,5-dihydro-5[1,4-dihydro-3-carbomethoxy-1,4-dioxo-5-methoxy-naphth-2-yl]4-hydroxyfuran-2(3H)-one (175) which could not be further utilised. Treatment of the furonaphtho-furanone (168) with aqueous potassium hydroxide and dimethyl sulphate afforded methyl[4-carbomethoxy-5,6-dimethoxy-naphtho[1,2-b]furan-2-yl] acetate (187). Structure assignment was confirmed by X-ray diffraction studies on the derivative 4-carbomethoxy-5,6-dimethyoxy-naphthol[1,2-b]furan-2-yl]acetic acid (192). The addition of the siloxyfuran to various naphthoquinones followed by treatment with dimethyl sulphate and potassium carbonate gave adducts with the 3(5-methoxy-2-furyl)-naphthalene ring system. Only 2-acetyl- 1,4,8-trimethoxy-3(5-methoxy-2-furyl)-naphthalene (196) was avialable in a synthetically viable yield. The derivatives 1,4,8-trimethoxy-3 (5-methoxy-2-furyl)-2-(trimethylsiloxy ethenylidene)naphthalene (198) and 2(2-iodo-1-oxo-1,2-ethanediyl)1,4,8-trimethoxy-3(5-methoxy-2-furyl)naphthalene (200) were readily prepared but none of these could be further manipulated towards the lactone precursor.