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

Abstract

Abstract:In this review the synthetic work in the field of aphidicolane, stemodane and stemarane diterpenoids, in which readily available (+)-podocarpic acid (4) was used as chiral template for the construction of their polycyclic structures, is described as it developed along the years. In the frame of this work (+)-podocarpic acid (4) was a very useful tool in a model study leading to the syntheses of tetracyclic ketones 7 and 8, models of key intermediates 5a and 6 in the syntheses of (+)-aphidicolin (1) and (+)-stemodin (2a), respectively. (+)-Podocarpic acid (4) was also converted into (+)-2-deoxystemodinone (2d), allowing confirmation of the stemodane diterpenoids absolute configuration, into (+)-aphidicol-15-ene (36) and into Stemodia chilensis tetracyclic diterpenoid (+)-19-acetoxystemodan-12-ol (2f), allowing confirmation of its structure. (+)-Podocarpic acid (4) was then extensively used in the work which led to the synthesis of (+)-stemar-13-ene (57) and (+)-18-deoxystemarin (3b). Finally, (+)-4 was converted into (+)-2-deoxyoryzalexin S (66), which made it possible to demonstrate that the structure of (+)-66 could not be attributed to a Chilean Calceolaria isolated diterpenoid to which this structure had been assigned.

Stemarane Diterpenes and Diterpenoids

“…This approach—which has been recently reviewed [75]—has been successfully accomplished and resulted in the synthesis from (+)-podocarpic acid of (+)-13-stemarene 12 and (+)-18-deoxystemarin 2 (Scheme 7) [14,76,77]. It was based on the inversion of configuration of the HO-C(12).…”

Aphidicolin: Its Chemistry and Biosynthesis

“…The readily available diterpenoid (+)-podocarpic acid has made a valuable chiral starting material for a number of syntheses in this area, and this work has also recently been reviewed. 62 A large number of derivatives of aphidicolin have been prepared in order to assess the relationship between structure and biological activity. [63][64][65]…”

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.…”