Chloropupukeananin, the First Chlorinated Pupukeanane Derivative, and Its Precursors from Pestalotiopsis fici

Abstract

Chloropupukeananin (1), the first pupukeanane chloride with highly functionalized tricyclo-[4.3.1.03,7]-decane skeleton and its possible biosynthetic precursors iso-A82775C (2) and pestheic acid (3), have been isolated from the plant endophyte Pestalotiopsis fici. The structure of 1 was determined by NMR spectroscopy and X-ray crystallography. Biogenetically, 1 could be derived from the Diels-Alder adduct of 2 and 3.

Chloropupukeanolides C–E: Cytotoxic Pupukeanane Chlorides with a Spiroketal Skeleton from Pestalotiopsis fici

“…These data hinted at a structural similarity of 8 to chloropupukeananin (1) [15] and chloropupukeanolides A (5) and B (6). [19] ]-decane moiety in 8 differs from that in 1 by having a ketal (d C = 107.0 ppm) instead of a ketone carbon (d C = 196.4 ppm) in position C10, thus featuring a spirocycle originating from the spirocarbon connecting a tricyclo-[4.3.1.0 3,7 ]-decane and a 5-hydroxy-7-…”

“…[19] In addition, this chlorinated tricyclo-[4.3.1.0 3,7 ]-decane moiety differed from that in 5 and 6 by having a C8 À C9 double bond ( 1 H COSY spectrum of 8 showed a cross-peak between H18 and 18-OH (d H = 5.25 ppm), indicating that the C18 oxygen of the isoprenylated 2,3-epoxycyclohex-5-en-1,4-diol is no longer acylated by a C26 carboxylic carbon of a 2,6-dihydroxy-4-methylbenzoate moiety, as in 1, [15] and a peroxide linkage between C6 and C18 as found in 5 and 6 [19] is also absent. These results were also supported by the upfield chemical shifts for the oxygenated carbons C6 (d C = 91.0 ppm in 8 vs. 108.4 ppm in 5) and C18 (d C = 67.5 ppm in 8 vs. 79.4 ppm in 5).…”

“…[31] Some neopupukeananes have also been isolated from marine sponges, such as 2-and 4-thiocyanatoneopupukeanane [30,32] and 9-isocyanoneopupukeanane. [33] Prior to the discovery of chloropupukeananin (1), [15] chloropupukeanolides A (5) and B (6), [19] and chloropupukeanone A (7), [19] the only example with a tricyclo-[4.3.1.0 3,7 ]-decane carbon skeleton from terrestrial sources was nemorosonol, a polyisoprenylated pupukeanane from the fruits of the South-American plant Clusia nemorosa and the leaves of the Vietnamese plant Garcinia bracteata (both of the Clusiaceae family). [35,36] Chloropupukeanolides C-E (8-10) are new chlorinated pupukeanane metabolites featuring a unique spiroketal skeleton derived from the highly functionalized tricyclo-[4.3.1.0 3,7 ]-decane and 2,6-dihydroxy-4-methylbenzoic acid moieties.…”

“…Thus, the above mentioned rearrangement of 9 to chloropupukeananin (1) turned out to be a substantial help. Since the absolute configuration of 1 was known from X-ray crystallography, [15] the configuration of 9 was deduced as 1S,3R,6S,7S,15S,16S,17R,18R, that is, opposite to that of 8 in the Southern part of the molecule (C1-C9), leaving open only the configuration at the remaining stereogenic center, C10 (see also the proposed biosynthetic pathway below).…”

“…[2][3][4][5][6][7][8][9][10][11][12][13][14] During the course of our continuing search for new bioactive natural products from this fungal genus, a subculture of P. fici (AS 3.9138 = W106-1), isolated from the branches of the tea plant Camellia sinensis (Theaceae) in the suburb of Hangzhou, Peoples Republic of China, was grown in different solid-substrate fermentation cultures. Chemical studies of the resulting crude extracts had afforded structurally unique natural products showing inhibitory effects on replication of HIV-1 virus in C8166 cells [15,16] including chloropupukeananin (1), [15] the first chlorinated pupukeanane analogue with a highly functionalized tricyclo-[4.3.1.0 3,7 ]-decane skeleton and its putative biosynthetic precursors 2 and 3 ( Figure 1), [15] and the pestaloficiols, [16] new 6,7-dihydroxy-5,6,7,8-tetrahydro-2H-chromen-4(3H)-ones possessing a cyclopropane moiety.…”