Facile Access to Optically Active Ring C Aromatic Diterpene Derivatives from (+)-Manool. First Synthesis of 13,14-Dihydroxy-8,11,13-podocarpatrien-7-one

Abstract

14,15,17-Trinorlabdan-8,13-dione 6 was efficiently synthesized via ozonolysis of (+)-manool (4) followed by treatment with aqueous NaOH in the presence of tetra- n-butylammonium bromide as catalyst. This protocol has the advantages of high yield, mild conditions and simple procedure. Utilizing this strategy, the first enantiospecific synthesis of 13,14-dihydroxy-8,11,13-podocarpatrien-7-one (1), a constituent of Taiwania cryptomerioides and Celastrus paniculatus, was achieved starting from (+)-manool (4) after a four-step sequence in 24% overall yield.

Synthesis of Novel Podocarpa-8,11,13-Triene-7- and 13-Nitriles and Evaluation of their Anti-Inflammatory and Cytotoxic Activity

“…The synthetic route used to achieve the target compounds is shown in Scheme 1. According to the procedure previously reported by us, the key intermediate 2 was obtained in two steps from (+)-manool 1, via ozonolysis 16 and intramolecular condensation, 17 and intermediate 3 was obtained in three steps from compound 2, via aromatisation, 16 protection 18 and benzylic oxidation. 18 Reaction of 3 with trimethylsilyl cyanide (TMSCN) in the presence of the KCN/18-crown-6 complex at room temperature for 8 h (Method A) followed by dehydration with POCl 3 gave compound 4 in 70% yield.…”

“…Only the podocarpa-13-nitrile 9 exhibited significant inhibition of NO production (IC 50 = 6 µM) but no cytotoxicity Scheme 1 (i) Ref. 16,17 (2 reaction steps); (ii) Ref. 16,18 activity in RAW 264.7 cells in the range of concentrations evaluated, as well as weak cytotoxic activity in HT-29 and PC3 cells.…”

“…16,17 (2 reaction steps); (ii) Ref. 16,18 activity in RAW 264.7 cells in the range of concentrations evaluated, as well as weak cytotoxic activity in HT-29 and PC3 cells. Thus, the inhibitory activity of the compound 9 could represent a new lead structure for the design of drug candidates against inflammatory diseases.…”

“…In view of the important applications of natural podocarpanes and related synthetic compounds with an aromatic ring C in 2014, our research group published the synthesis of a series of podocarpane derivatives with cytotoxic activity. 16 In this study, in order to discover new substances with anti-inflammatory activity, we have prepared some podocarpa-8,11,13-triene-7-and 13-nitriles (4-10) from the naturally occurring labdane diterpenoid (+)-manool 1, using podocarp-8( 14)-en-13-one 2 and 13-methoxypodocarpa-8,11,13-trien-7-one 3 as key intermediates. The partial syntheses, in vitro inhibition of NO production and cytotoxicity in a mouse macrophage cell line (RAW 264.7), as well as cytotoxicity against two human adenocarcinoma cell lines (colon: HT-29 and prostate: PC3) are reported here.…”

Enantioselective total syntheses of six natural and two proposed meroterpenoids fromPsoralea corylifolia

“…The selective removal of methyl phenol ether was then examined, and the expected phenol 11 was obtained in excellent yield (93%) using the PhSH/K 2 CO 3 /NMP reaction system. 16 To install an OH group at the C-3 position of the aryl ring, a two-step one-pot transformation 17 involving IBX-mediated oxidation and subsequent reduction of the resultant ortho diketone with NaBH 4 yielded the proposed corypsoriol J (1c) (95% yield) ( Scheme 2 ). Unfortunately, the spectral data of synthetic corypsoriol J were not consistent with the reported ones of the natural product.…”