Regio- and Diastereoselective Synthesis and X-ray Structure Determination of (+)-2-Deoxyoryzalexin S from (+)-Podocarpic Acid. Structural Nonidentity with Its Nominal Natural Isolated Enantiomer

Abstract

(+)-2-Deoxyoryzalexin S (1), the nominal enantiomer of a diterpenoid isolated in Chile from Calceolaria species, was regio- and diastereoselectively synthesized from (+)-podocarpic acid. (+)-2-Deoxyoryzalexin S (1) was characterized also as its acetyl derivative, (+)-2, whose structure was confirmed by X-ray crystallographic analysis. Surprisingly, comparison of the data recorded for (+)-1 and (+)-2 and those reported in the literature for the Calceolaria isolated diterpenoid 1 and its derivative (-)-2 showed some differences, suggesting that the latter do not possess the proposed structures.

(+)-Podocarpic Acid as Chiral Template in the Synthesis of Aphidicolane, Stemodane and Stemarane Diterpenoids †

“…(+)-Podocarpic acid (4) was then extensively used in the work which led to the synthesis of (+)-stemar-13-ene (57) and (+)-18-deoxystemarin (3b) [55,56,59,60,62]. (+)-Podocarpic acid (4) was also converted into (+)-2-deoxyoryzalexin S (66) [69]. The latter work also allowed us to demonstrate that the structure of (+)-2-deoxyoryzalexin S (66) cannot be attributed to a Chilean Calceolaria isolated diterpenoid.…”

“…The latter dissolved in toluene was heated at 85 °C in the presence of TsOH, giving (+)-77 (see Section 8.6). Thioacetalization of (+)-77 by standard methods followed by deoxygenation gave then (+)-2-deoxyoryzalexin S (66) which was then acetylated to (+)-79 [69]. The relative configuration of (+)-79 was confirmed by an X-ray structure determination.…”

“…The latter dissolved in toluene was heated at 85 °C in the presence of TsOH, giving (+)-77 (see Section 8.6). Thioacetalization of (+)-77 by standard methods followed by deoxygenation gave then (+)-2-deoxyoryzalexin S (66) which was then acetylated to (+)-79 [69]. Finally, having in hand an efficient methodology for the construction of the C/D ring system of stemarane diterpenoids, we decided to apply it to the synthesis of (+)-2-deoxyoryzalexin S (66), the structure and absolute configuration of which had been established only on the basis of the corresponding 1 H-and 13 C-NMR spectra [66][67][68].…”

Unexpected Racemization in the Course of the Acetalization of (+)-(S)-5-Methyl-Wieland–Miescher Ketone with 1,2-Ethanediol and TsOH under Classical Experimental Conditions

“…In the course of our work on bioactive natural products and bioactive materials [117][118][119][120][121][122][123][124], it occurred to us to observe the partial racemization of (+)-5 during the acetalization of (+)-1 with 1,2-ethanediol and TsOH in the presence of a Dean-Stark apparatus. According to our best knowledge, obtaining partially racemized (+)-5 or (−)-5 when the acetalization reaction is carried out by this procedure on (+)-1 or (-)-1 [33,35,39,40,44,48,49,72,77,81,84,87-91,116], respectively, has not been previously reported in the literature, which was the reason behind investigating this reaction.…”

“…According to our best knowledge, obtaining partially racemized (+)-5 or (−)-5 when the acetalization reaction is carried out by this procedure on (+)-1 or (-)-1 [33,35,39,40,44,48,49,72,77,81,84,87-91,116], respectively, has not been previously reported in the literature, which was the reason behind investigating this reaction. In the course of our work on bioactive natural products and bioactive materials [117][118][119][120][121][122][123][124], it occurred to us to observe the partial racemization of (+)-5 during the acetalization of (+)-1 with 1,2-ethanediol and TsOH in the presence of a Dean-Stark apparatus. According to our best knowledge, obtaining partially racemized (+)-5 or (−)-5 when the acetalization reaction is carried out by this procedure on (+)-1 or (-)-1 [33,35,39,40,44,48,49,72,77,81,84,[87][88][89][90][91]116], respectively, has not been previously reported in the literature, which was the reason behind investigating this reaction.…”