Twelve Novel and Diverse 16-Norphragmalin-Type Limonoids from Chukrasia tabularis var. velutina

Abstract

A series of novel and structurally related C-15-acyl 16-norphragmalin-type limonoids, chuktabrins C-J (1-8) and chuktabularins U-X (9-12), were isolated from the stem bark of Chukrasia tabularis var. velutina. Their structures were established on the basis of detailed spectroscopic analysis, and the absolute configuration of compound 1 was determined by a single-crystal X-ray study using a mirror CuKα radiation. Compounds 7 and 8 were unprecedent C-15-acyl 16-norphragmalins with ketonic alkyl appendage at C-15, and compounds 4 and 8 were first examples of limonoid with a characteristic carbonate moiety esterified at OH-9/OH-8 or OH-1/OH-8 respectively. A biosynthetic pathway of these limonoids was reasonably presumed based on the novel and diverse structures isolated, which provides a new insight into the plausible biosynthesis of C-15-acyl 16-norphragmalin-type limonoids. The anti-inflammatory activity of major isolates were evaluated for inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophage (RAW264.7) cell line, with IC 50 value ranging from 2.40 to 16.90 μM.

Two New Phragmalin-Type Limonoids from Chukrasia tabularis var. velutina

“…Thus, these correlation required the presence of -OR substituent at C-8, C-9 and C-30. The 13 C-NMR data for C-30, C-9 and C-8 were similar to those for chuktabrin C, which was determined by single-crystal X-ray diffraction [ 8 ], determining the position of enol ether at C-30 and the carbonate moiety at C-8 and C-9.…”

“…The key ROESY correlations ( Figure 3 ), from H-5 to H-11, H-17, and H-21, H-17 to H-5, H-11, H-21, and H-30, Me-18 with H-14 and H-22, H-29a with H-3, and H-29b with H-19b, indicated that the relative stereochemistry of the key asymmetric carbons of 1 was well matched with those of chuktabrin C obtained by X-ray crystallography [ 8 ]. Thus, the structure of 1 was established as shown in Figure 1 , namely as a 12-deacetyl derivate of chuktabrin H [ 8 ].…”

“…, three upfield proton signals at δ H 6.42, 7.59, and 7.68 and a set of double proton signals at δ H 1.92 and 1.46 with an 11.0 Hz coupling constant in the 1 H-NMR ( Table 1 ), and four olefinic carbons at δ C 109.9, 121.5, 141.1, and 143.7 in the 13 C-NMR ( Table 1 ), indicated that compound 1 was a phragmalin-type limonoid possessing an α,β-substituted furan ring and a 4,29,1-bridge moiety [ 8 ]. The presence of a carbon signal at δ C 92.4 showing a HSQC correlation with the proton signal at δ H 4.67 and two down-field carbon signals at δ C 152.0 and 152.8 suggested that compound 1 was a 16-norphragmalin with an enolic alkyl appendage at C-15 and a characteristic carbonate moiety like chuktabrins C-H [ 8 ]. The obvious HMBC correlations ( Figure 2 a) from a set of ethyl proton signals [δ H 2.10, q, (7.5), 2H; δ H 1.04, t (7.5), 3H] and proton signal of H-15 (δ H 4.67) to a carbon signal at δ C 152.8 (C-1') indicated that a propionyl group was attached at C-15 biosynthetically as in the chuktabrins C-H [ 8 ].…”

“…The presence of a carbon signal at δ C 92.4 showing a HSQC correlation with the proton signal at δ H 4.67 and two down-field carbon signals at δ C 152.0 and 152.8 suggested that compound 1 was a 16-norphragmalin with an enolic alkyl appendage at C-15 and a characteristic carbonate moiety like chuktabrins C-H [ 8 ]. The obvious HMBC correlations ( Figure 2 a) from a set of ethyl proton signals [δ H 2.10, q, (7.5), 2H; δ H 1.04, t (7.5), 3H] and proton signal of H-15 (δ H 4.67) to a carbon signal at δ C 152.8 (C-1') indicated that a propionyl group was attached at C-15 biosynthetically as in the chuktabrins C-H [ 8 ].…”

“…The stem barks of plants of the genus Chukrasia , traditionally used in Southern China to treat cold and fever [ 1 ], have been a research focus for natural products chemistry in recent years, and a series of phragmalin-type limonoids with novel and diverse structures have been isolated [ 2 , 3 , 4 , 5 , 6 ]. In our previous research on limonoids from the stem barks of the title plant, many kinds of phragmalins with different skeletons were isolated, such as 16-norphragmalin with ketonic, enolic, or ketal alkyl appendages at C-15 [ 5 , 7 , 8 , 9 ], phragmalin orthoesters with enolic alkyl appendages at C-15 [ 10 ], phragmalin with an unprecedented 8-oxatricyclo [ 4 , 3 , 11 , 6 ] decane moiety [ 11 ], and normal phragmalin and its orthoester derivative [ 12 , 13 , 14 , 15 , 16 ]. Further investigation on the phragmalin-type limonoids of this plant led to the isolation of two new phragmalin-type limonoids ( Figure 1 ) with different structural skeletons.…”