Diels–Alder Reaction of Levopimaric Acid with 2-(2,4-Dioxo-5-Thiazolidinylidene)Acetic Acid

Abstract

New derivatives of levopimaric acid containing a thiazolidinedione fragment were synthesized by a Diels-Alder reaction of levopimaric acid and 2- (2,4-dioxo-5-thiazolidinylidene)acetic acid. The new compounds were characterized using elemental analysis and NMR spectroscopy.Publications on the synthesis of diene adducts of resin acids have grown dramatically in the last few years. Compounds with antitumor, anti-inflammatory, antiulcer, and antiviral activity were found among diene adducts of levopimaric acid with quinones [1]. Syntheses of thiazole and its derivatives were widely explored because of the large number of natural products and drugs with that heterocycle in their structures [2,3]. Thiazolidinedione derivatives exhibit anti-inflammatory [4], antibacterial [5], antituberculosis [6], antifungal [7], and anti-HIV [8] activity. The diene synthesis of levopimaric acid and 2-(2,4-dioxo-5-thiazolidinylidene)acetic acid seemed interesting with respect to the discovery of new optically active compounds with potential biological activity.In continuation of research on the synthesis of new levopimaric acid derivatives [9, 10], we performed a Diels-Alder reaction of levopimaric acid (1), which occurs in pine sap (~30%), with 2-(2,4-dioxo-5-thiazolidinylidene)acetic acid. The reaction after 17 d was stereoselective and formed two regioisomers 2a and 2b in 81% yield. The ratio of 2a:2b was 7:1 and was established using the integrated intensity of the H-1 singlet in PMR spectra. Unfortunately, we were unable to separate the mixture of regioisomers and isolate pure major isomer 2a.Methylation of the mixture of 2a and 2b by diazomethane produced N-methyl dimethyl esters 3a and 3b in quantitative yield. Purification by column chromatography isolated pure major diester 3a.Structures of all synthesized compounds were established using NMR spectroscopy and elemental analysis. COSY, TOCSY, NOESY, 1 H-13 C HSQC, 1 H-13 C HMBC, and 1 H-15 N HMBC spectra were recorded in order to assign accurately resonances of framework atoms. 13 C NMR spectra were interpreted based on . Chemical shifts for protons of corresponding C atoms were established using HSQC spectra. Coupling of geminal and vicinal protons were confirmed by 1 H-1 H COSY spectra; through-space coupling of protons with geminal and vicinal C atoms, HMBC spectra.

[3+2] Cycloaddition of N‐benzylazomethine Methylide with Various Arylidene‐Azolones

“…[19][20][21] In particular, cycloaddition of various azolones with exocyclic double bond is very promising strategy for the creation of spirocyclic core (Scheme 2). [20,[22][23][24][25][26][27] Among others, such a simple and readily available reagent as N-benzyl-1-(trimethylsilyl)-N-(methoxymethyl)methanamine (compound I, Scheme 2), which easily generates N-benzylazomethine methylide, is of special interest. [15,28,29] It is used for the synthesis of tetrahydropyrroles (pyrrolidines) that are unsubstituted at the second and fifth positions.…”

Heterologous production of levopimaric acid in Saccharomyces cerevisiae

“…Some plant origin diterpenes are even found to have industrial applications, such as taxol mainly from Taxus brevifolia [ 4 ], tanshinones [ 5 ] from Salvia miltiorrhizha , and ambroxan from Salvia sclarea [ 6 ]. LA, an important diterpene resin acid in conifers, is a significant industrial intermediate; its Diels–Alder reaction products are widely used in coatings, printing inks, plasticizers and adhesives [ 7 , 8 ]. However, these high value-added terpenoids rarely accumulate in their native host and are difficult to chemically synthesize due to their complicated chemical structure.…”