Synthesis of 3‐0‐o.coumaryl‐, 4‐0‐o.coumaryl‐and 3‐0‐ferulyl‐d‐(‐)‐quinic acid. Improved synthesis of 3‐0‐sinapyl‐d‐(‐)‐quinic acid

Abstract

The title compounds were obtained by a reaction sequence starting from diphenylmethyl 4,5-0-isopropylidenequina$e. Suitably protected cinnamyl chlorides were condensed with this compound, followed by reaction of the intermediate esters with hydrazine hydrate, and then with acetic acid-formic acid-water. The total yields of 3-0-o. As already mentioned in the foregoing paper ( 5 ) . the synthesis of the title compounds by the method proposed by HASLAM et a2 for the synthesis of e.g. 3-O-p.coumaryl-D-(-)-quinicacid (1x)(6), gave rather disheartening results. In fact, the final removal of the protective functions from the easily prepared intermediates (e.g. V I ) required prolonged acidic treatment, entailing heavy losses of material. However, a s this requirement could be explained by the high stability of the employed 1-0-ethoxycarbonyl-protection (as in VI) in acidic medium, it seemed worthwhile to investigate a synthetic procedure based on the use of diphenylmethyl 4,5-0-isopropylidenequinate (II), a compound without any protection on the 1-hydroxyl-function. This approach looked promising, because in I1 a marked difference towards acid chlorides between the sterically hindered, axial tert. alcohol group on C-1 and the equatorial sec. alcohol group on C-3 may be expected (see e.g. ( 7 -1 0 ) ) .The results obtained confirm the validity of this supposition. The procedure, followed for the synthesis of the title compounds VIII, XI and XI1 is depicted in the scheme.-663 -

Synthesis of p -coumaroylquinic acids and analysis of their interconversion

“…The crude product was esterified following the same protocol as with 1 and purified by column chromatography to give compound 8 in 48% yield. Protection of the hydroxyl group was not necessary since Pooter et al demonstrated that under mild conditions no esterification occurs at the axial C-1 hydroxyl group of quinic acid 27. Deprotection was performed in 6 days in the presence of HCl (2N)/ THF to obtain 5-O-p-coumaroylquinic acid 2a in 77% from the protected ester 8.…”