Synthesis of Naturally Occuring 2,5-Dialkylchromones. Part 1. Synthesis of Aloesone and Aloesol

A number of 2-alkyl-7-alkoxy (or hydroxyl-5-methylchromones.including naturally occurring aloesone and aloesol, Were synthesized starting from ethyl orsellinate y & 0-ketosulfoxides as intermediates.In connection with our studies on the constituents of aloe1, the dried latex of the leaves of Aloe spp.2, we needed substantial amounts of 2-acetonyl-7-hydroxy- 5-methylchromone ( s ) .This compound, commonly known as aloesone, has been 3 reported to be present in a few species of Aloe .It might be a biosynthetic precursor of the C-glucosylchromones occurring in + ~pp.''~, but no experiments 5 have so far been reported on the in vivo C-glucosylation of the chromone nucleus .In addition, other 5-methylchromones, e.g.Ib and (S)-12, have recently been -7found in Polygonurn cuspidatum6 and in rhubarb .Thus, a convenient synthesis of la and related compounds appeared to be desirable in order: i) to use them as & reference standards in routine analyses of commercial samples, iil to evaluate their physiological properties8, and iii) to prepare properly labelled samples for precursor-incorporation experiments.This paper deals with a general procedure to obtain 2-alkyl-7-alkoxy lor bydroxyl-5-methylchromones (3 and particularly describes the first total synthesis of aloesone I and 1R.S)-aloesol (121.9Ethyl orsellinate (5) was prepared according to Sonn's method , i.~.y & Claisen condensation between ethyl acetoacetate and methyl crotonate followed by hromination of &to 3 -and reductive dehalogenation of the aromatic ring (Scheme 1). 4 was then selectively protected at the 4-hydroxyl function by treatment with d methyl iodide or 6-methoxyethoxymethyl IMEM) chloridelo, taking advantage of the presence of a strong intramolecular hydrogen bond between the ethoxycarbonyl group and the hydroxyl function in --position.The construction of the y-pyrone ring to complete the chromone nucleus was achieved using 6-ketosulfoxides 6a.2 as key intermediates1'.They were prepared by condensation of the (4-OH)-protected ethyl orsellinate, i.~.2.2. with sodium methylsulfinylmethidel 'I ' .