Kung-Kai Cheung

A rearranged hydroperoxide from the reduction of artemisinin

Abstract Lithium aluminium hydride reduction of artemisinin produces two unexpected rearrangement products in addition to those reported previously. The structure of the major rearrangement product, a tertiary hydroperoxide, was determined by 2D-NMR and chemical reactions. A mechanism is proposed for this rearrangement, based on the observation that dihydroartemisinin can also be converted into the same hydroperoxide in alkaline solution.

Structure elucidation of arteannuin O, a novel cadinane diol from Artemisia annua, and the synthesis of arteannuins K, L, M and O

Abstract The novel cadinane diol, arteannuin O (1), has been obtained from Artemisia annua and its structure has been established by 2D NMR and X-ray crystallography. A reconstructive synthesis of arteannuin O from artemisinin is described, which also yields the natural products arteannuin K and arteannuin L. Mechanistic considerations have led to the conclusion that the stereochemistry of the 5-hydroxyl group was wrongly assigned when arteannuins K, L and M were first reported as natural products. This was confirmed by derivatization of synthetic arteannuins K, L and M as their Mosher esters.

First synthesis of spiro[benzofuran-2,1′-isobenzofuran]-3,3′-dione and its X-ray crystal structure

The title compound has been synthesised by selenium dioxide oxidation of 2′-carboxy-2-hydroxy-deoxybenzoin 3 and its structure has been confirmed spectroscopically and by X-ray crystallography. An earlier report of this compounds synthesis is shown to be erroneous. The synthesis of 3-(2-hydroxyphenyl)isoquinolin-1 (2H)-ones from 2′-carboxy-2-hydroxydeoxybenzoin 3 is also described.

Oxazolo[3,2-a]indoles, pyrrolo- and azepino-[1,2-a]indoles from 3H-indole 1-oxides and acetylenecarboxylic esters by skeletal rearrangements

3H-Indole N-oxides 3 have been prepared from 3H-indoles 1 by hydride reduction followed by mchloroperbenzoic acid oxidation. Reaction of 3 with dimethyl acetylenedicarboxylate (DMAD) and with methyl propiolate (MP), give a variety of products, all apparently formed by rearrangement of the initial isoxazole 1,3-dipolar cycloadduct, with the type of reaction being dependent on the 2substituent in 3: the 2-phenyl derivative of 3 gives oxazolo[3,2-a]indoles 5, and when 3 posseses a methyl or methylene substituent at C-2, both DMAD and MP give pyrrolo[1,2-a]indoles 6, with the MP reactions also yielding an azepino[1,2-a]indole 7 in each case. The structures of the products have been established by spectroscopy with those of 5b and 7b being confirmed by X-ray crystallography.

Synthesis of α-Corocalene

α-Corocalene, a constituent of hop oil, has been synthesized in four steps from the monoterpene (+)-pulegone.

The synthesis of various cycloalkana[d]xanthones and conversion of the cyclohexa-analogue to a 7,7a-dimethylcyclohexa[d]xanthene†

The synthesis of cyclo-penta-, -hexa- and -hepta-[d]xanthones 5 from (E)-(2-hydroxyphenyl)-5-arylpent-4-ene-1,3-diones 4, cycloalkanones and pyrrolidine is described. Reactions to modify 5 in an attempt to synthesize analogues of the five naturally occurring cyclohexa[d]xanthenes (with general formula 1) are also described: these reactions include C-methylations at C-7 and C-7a, hydride reduction of the 8-keto group, dehydroxylations and finally catalytic reduction to give 16. The stereochemistry of 16 established by NOE and an X-ray crystal structure of 9aB differs from 1 at two contiguous C-atoms.

Reactions of 5-Methyl-6-thioxo-5,6,11,12-tetrahydrodibenzo[b,f]azocin-12-one and a Novel Rearrangement to a Hydroximino-isothrochromene

The synthesis of dibenzazocinone 2 and several of its reactions are described, including formation of a benzylidene derivative 3, which with hydroxylamine undergoes a novel rearrangement to give the methanone 8.

A novel synthesis of cyclopenta- and cyclohexa-[d]xanthones from the reaction between cycloalkyl enamines and 2-hydroxyphenylpentene-1,3-diones, and their rearrangement to cyclopenta- and cyclohexa-[a]xanthones

Treatment of (E)-5-substituted-1-(2-hydroxyphenyl)pent-4-ene-1,3-diones 1 with alicyclic ketone enamines 2 rapidly gives the cycloalkano[d]xanthones 3, but on longer treatment or on reaction of 3 with base, cycloalkano[a]xanthones 4 are obtained; their structures, including stereochemistry, were determined from spectrosopic data and, in the case of 3aB, from X-ray diffraction analysis.

Reactions of an indeno[1,2-b]indole and novel rearrangements of a dioxodibenz[b,f]azocine to derivatives of 5,12-diaza- and 5-oxa-12-aza-chrysene

Oxidation of 10-benzylidene-5-methyl-5,10-dihydroindeno[1,2-b]indole (2) gives the dioxodibenz[b,f]azocine (3), which reacts (probably via a transannular interaction) with hydroxylamine and with ethylamine to give oxa-aza- and diaza-chrysene derivatives (5) and (6); the X-ray crystal structure of (5) is reported.