Desmond M. S. Wheeler

SYNTHESIS OF A RING A PRECURSOR OF DOXORUBICIN : STEREOSELECTIVE CONTROL OF THE EPOXIDATION OF A HOMOALLYLIC ALCOHOL BY HYDROXYL AND ESTER GROUPS

Abstract The key step in a synthesis of a precursor for ring A in doxorubicin is the stereoselective control of the epoxidation of a homoallylic alcohol by ester and hydroxyl groups; the result leads to a new method of forming lactones in excellent yields under neutral conditions.

Effects of bleached and unbleached rosemary oleoresin and rosmariquinone on light-sensitized oxidation of soybean oil

Synthetic rosmariquinone (RQ), an antioxidant naturally present in rosemary (Rosmarinus officinalis L.), tertiary butylhydroquinone (TBHQ) and rosemary oleoresin (bleached and unbleached), was tested for antioxidant activity in stripped and nonstripped soybean oil in a light-induced oxidation system. In the stripped soybean oil system, RQ was significantly less (P<0.05) effective than TBHQ at controlling oxidation of the oil. In light-induced oxidation of nonstripped soybean oil, RQ had significantly lower (P<0.05) peroxide values (PV) than TBHQ after 36 h. RQ had PV that was significantly (P<0.05) lower than those for both the bleached and nonbleached rosemary oleoresin throughout the 72-h study.

An Efficient Steric Controlled Photo-Fries Rearrangement in the Naphthalene Series

Abstract For the work on the synthesis of 2-acyl-5-methoxynaphthoquinones as tricyclic analogues of daunomycinone1, we wanted to develop an efficient regioselective synthesis of 5-methoxy-2-acyl-1-naphthols without using Lewis acids. This requirement precluded the use of the thermal Fries but not the photo-Fries rearrangement. Although the mechanistic aspects of the photo reaction have received much study2, the reaction has been little used preparatively3 because it usually gives poor yields of hydroxy ketones even when only one product is possible.

Structure and reactions of photothebainehydroquinone

Abstract The structure of photothebainehydroquinone, which was obtained by unsensitized irradiation with UV light of thebainequinone ( 1 ) or thebainehydroquinone ( 2 ) has been shown by X-ray crystallography to be 3a , which arises from 2 through a di-π-methane to vinylcyclopropane rearrangement. Treatment of 3a with acid gave 5a, 6a, 5b and probably 6b . Studies using DCl showed that the opening of the cyclopropane in 3a to give 5a, 5b , and 6a involved ‘end-on’ approach of the D + . The mechanisms of the reactions are discussed.

An Efficient Stereoselective Synthesis of a Tricyclic Intermediate for the Synthesis of Derivatives of Abietic and Podocarpic Acids

Abstract For many years the synthesis of diterpene acids has attracted the attention of organic chemists. Kroniger and Wheeler1 reported that the condensation of the dimethylate 1a with methyl malonate gave the cis compound 2a which on heating with palladised charcoal was converted into the trans isomer 3a. Compound 3a is a promising intermediate in the synthesis of derivatives of both abietic and podocarpic acids, while 2a could be a starting material for the synthesis of cis fused diterpene acids. However, the route to 2a and 3a was inefficient; 1a was only available as the minor component of a mixture with its epimer 1b; and the yield for the stage 2a + 3a was poor.

Synthesis of diterpenoid acids—XI: Cyclizations with malonic ester

Abstract The dimesylate of one of the epimeric 1-methyl-1-(3′-hydroxypropyl)-2-cyclohexanols reacts with malonic ester to give cis -1,1-dicarboalkoxy-4-methyldecalin. Similarly, the dimesylate of one of the epimeric 1-methyl-1-(3′-hydroxypropyl)-1,2,3,4-tetrahydro-2-naphthols condenses with malonic ester to give cis -1,1-dicarbomethoxy-4a-methyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene. This product on heating with palladized charcoal gave the trans isomer. A number of derivatives of the cis -fused products have been prepared. A study of the NMR spectra of the cyclization products and some of their derivatives and other data shows that the trisubstituted bicyclic compounds exist mainly in a conformation in which the angular methyl group is in a 1,3-diaxial relation to an ester group, while with the trisubstituted tricyclic compounds the major conformation is one in which there is no 1,3-diaxial relation between the angular methyl and an ester.

Base-catalysed rearrangement of thebainehydroquinones.

Abstract On the basis of spectra and pKa values structures are assigned to the monomethyl ethers of thebainehydroquinone. Thebeinehydroquinone (1a) and its 21-methyl ether (1b) rearrange under basic conditions to the corresponding flavothebaones (2a and 2c). The 18-methyl ether (1c) does not rearrange. A mechanism involving a cyclopropane intermediate is proposed for the rearrangements.

A novel stereoselective synthesis of the ring AB podocarpate system

A new way of stereoselectively synthesizing rings A and B of podocarpate has been developed; the correct stereochemistry at C4 is obtained during a cyclization linking C2 to C3.

The Reaction of Coumalic Acid with Benzoquinone: Formation of a Spirobutenolide

Abstract Although additions of α-pyrones to dienophiles have received extensive study,1 there have been few reports of additions of α-pyrones to quinones.2 In attempts to add benzoquinone (1) to coumalic acid (2), we have found that keeping these compounds in methanol and acetic acid in the presence of sodium acetate for 4 hours at 0°C followed by removal of the solvents under reduced pressure and purification by flash chromatography gave compound 3 3 (22%4) mp 158–161°C raised to mp 160–162°C (benzene) UV (MeOH) λ;306 nm (∊ 4700), 215 (12,500); IR (CHCl3) vmax 3340, 1770 cm−1; 1H NMR ((CD3)2CO) δ 3.5 (s, 3H), 5.52 (s, 1H), 6.35 (d, J=5 Hz, 1H), 6.55 (m, 1H), 6.85 (m, 2H), 7.55 (d, J=5 Hz, 1H); 13C 171.5, 153.8, 153.4, 150.9, 122.3, 121.8, 119.6, 111.8, 110.8, 94.7, 56.9; mass specteum m/e (relative intensity) 234.0530 (54), 202.0267 (100), 174.0320 (34), 146.0367 (88), 98.0371 (47); m/e calcd for C12H10O5.

Preparation of a 4-monoketal of juglone methyl ether

Abstract Oxidation of 5-methoxy-1-naphthol with thallium trinitrate in ethylene glycol/trimethylorthoformate gives the 4-ethylene ketal of juglone methyl ether.