Synthesis and phytotoxicity evaluation of novel 6α,7β-dihydroxyvouacapan-17β-oic acid derivatives

Abstract

The 6a,7b-dihydroxyvouacapan-17b-oic acid (1) isolated from Pterodon polygalaeflorus Benth has shown allelopathic and plant growth regulatory properties. Six novel esters of (1) were prepared and their effects on the radical growth of Sorghum bicolor L. and Cucumis sativus L. were evaluated.The natural product 6a,7b-dihydroxyvouacapan-17b-oic acid (1) and the lactone 2 (Scheme 1), exhibit anti-inflammatory, analgesic activities, 1 and allelopathic activity. 2 Several terpenoids are involved in plant allelopathic interactions but little is known about the effects of diterpenes on plant growth regulation. 3,4 Some derivatives of 1 have been prepared for biological evaluation. 2,5,6 Here we report the preparation of the esters 4-9 (Scheme 1), and an evaluation of their phytotoxic properties.The acid (1) was isolated from the P. polygalaeflorus Benth fruits. 7 The d-hydroxy-lactone 2 5 and d-keto-lactone 3 8 were prepared as shown in Scheme 1. The novel compounds 4-9 were prepared in good yields (77-89 %) using catalytic amounts of NaOH. The lactone 3 is not very soluble in the alcohols. Thence the end of the reaction could be observed by TLC and by the total disappearance of the solid phase.The esters 4-9 were characterised by elemental analysis, IR and NMR spectroscopy. The IR spectra of all the esters 4-9 showed a hydroxyl absorption between 3495 and 3465 cm -1 and strong C=O stretching bands in the 1735-1709 cm -1 range due to the ester and ketone groups. In the 13 C NMR spectra, the carbonyl signals were observed around d C 174 (ester) and d C 209 (ketone). The 1 H NMR signals due to the furanditerpene backbone hydrogens of the esters 4-9 are very similar to those observed in the spectrum of the parent lactone 3. 8 It is interesting to note the multiplicity of the signal at d H 1.70 in the 1 H NMR spectrum of 6 which is a sextet assigned to H-2', indicating non-resolvable coupling constants (J 7.3 Hz)with the theoretically non-equivalent hydrogens H-1' and H-3'. Other features worth mentioning are the nonequivalence of the H-1' methylenic hydrogens revealed by the double doublets observed in the 1 H NMR spectrum of compound 9 at d H 4.61 and 4.71 with Jgem 12.2 Hz and Jvic 7.2 Hz with H-2'. The remaining signals were in accordance with the proposed structures.It was previously reported that 1 at 100 ppm inhibited the root growth of Sorghum bicolor L. (30-40 %) and stimulated Cucumis sativus L. (5-10 %). 2 Recently it was shown that lactones 2 and 3 inhibited the uncoupled noncyclic electron transport and ATP synthesis, behaving as Hill reaction inhibitors, and the carbonyl at C-6 of 3 affected the photophosphorylation. 2,8 Compounds 1-9 were evaluated in vitro against S. bicolor and C. sativus using a different methodology. 9 As the compounds were not soluble in the usual formulations, 9 an aqueous solution of a triblock copolymer and DMSO was used instead. Table 1 shows the radical lengths. Under these conditions, the novel compounds and the parent lactones did not significantly affect the growth of S. bicolor.

Theoretical and experimental NMR studies of the Swern oxidation of methyl 6α,7β-dihydroxyvouacapan-17β-oate

“…IR (KBr) m max /cm -1 3500, 2980, 2820, 1750, 1720, 1460, 1420, 1390, 1260, 1130, 1050, and 760. NMR data of 4 are in agreement with the literature[8,27]. Methyl 6a-hydroxy-7-oxovouacapan-17b-oate(5): 1 H NMR (400 MHz; CDCl 3 ) d H 7.24 (m; H-16), 6.29 (d, J = 1.2 Hz; H-15), 4.48 (dd, J = 12.7 and 3.9 Hz; H-6), 3.93-3.85 (m; H-14), 3.79 (s; OCH 3 ), 3.66 (d, J = 3.9 Hz; OH), 3.19 (dd, J = 12.2 and 10.2 Hz; H-9), 2.74 (dd, J = 16.1 and 4.7 Hz; H-11a), 2.63-2.50 (m; H-11b), 1.80-1.70 (m; H-8), 1.70-1.50 (m; H-2a and H-2b), 1.60-1.40 (m; H-3a), 1.30-1.15 (m; H-3b), 1.29 (s; H-20), 1.27-1.20 (m; H-1b), 1.23 (d, J = 12.7 Hz; H-5), 1.17 (s; H-19), 1.15 (s; H-18), and 1.13-1.00 (m; H-1a).…”

“…Similarly, the signals of hydroxyl groups at d H 3.64 (OH-7) and 3.66 (OH-6) of 4 and 5, respectively, were absent. Furthermore, the signals at d H 0.95, 2.18, and 1.23 (corresponding to H-5 of 2, 4, and 5, respectively) were also absent [8]. On the other hand, a signal at d H 6.52, attributed to an enol group, was observed.…”

“…2. Compound 4 was previously obtained by transesterification of 6-oxovouacapan-7b-17b-lactone [8], while 5 is a new compound.…”

“…Among these compounds, 6a,7b-dihydroxyvouacapan-17b-oic acid (1) and its methyl ester (2) have been obtained ( Fig. 1) [7,8]. Analgesic and anti-inflammatory activities have been observed for compound 1 [9][10][11].…”

Phytotoxic Diterpenoids from Plants and Microorganisms

“…It could inhibit the root growth of Sorghum bicolor with the inhibition rates ranging from 30 to 40 % and stimulate the root growth of C. sativus about 5–10 %. Compounds 178 – 181 ( Figure ) were prepared via the chemical modification and their phytotoxic activity was also evaluated . Compound 178 inhibited the radicle growth of C. sativus with an inhibition rate of 32 %, while compounds 179 and 180 stimulated the root growth of C. sativus ranging from 9 to 19 %.…”