Total Syntheses of the Gregatins A–D and Aspertetronin A: Structure Revisions of These Compounds and of Aspertetronin B, Together with Plausible Structure Revisions of Gregatin E, Cyclogregatin, Graminin A, the Penicilliols A and B, and the Huaspenones A and B

Abstract

Comprehensive comparisons of 1H and 13C NMR chemical shift values in the furanone cores a, b, and c provide plausible support for a reassessment of the furanone nuclei of the title compounds from b to c. Total syntheses via enantiomerically pure lactic esters were based on the Seebach–Fráter “self‐reproduction of stereocenters” methodology. Attachment of the hexadienyl side‐chain in a trans,trans‐selective manner was achieved by addition of the Seebach–Fráter enolate to trans‐hex‐4‐en‐1‐al rather than to trans‐hex‐3‐en‐1‐al. The type‐c furanone cores of the synthetic materials were reached by single or double acylation of a model γ‐hydroxy‐β‐oxo ester (compound 50) and its hexadiene‐containing counterpart 29. Our syntheses confirmed the novel connectivities in six compounds. In addition, they required revision of the configuration of a quaternary carbon atom in five cases. Moreover, they allowed elucidation of the configurations of four previously unassigned stereocenters. Hindsight analyses of why the furanone cores of the title compounds had been misinterpreted as a and/or b instead of c are given. Why the stereocenters in the heterocycles had been incorrectly configured, on the bases (a) of relay studies in the 1960s, and (b) of a 1984 total synthesis of gregatin B, is also discussed.

Paraconfuranones A–H, eight new furanone analogs from the insect‐associated fungus Paraconiothyrium brasiliense MZ‐1

“…However, the tertiary carbon for C3 in compound 1 was converted to be a quaternary carbon in compound 5 according to the 13 CNMR spectrum and DEPT 135 spectrum, implying the existence of a substituent group at C3 in compound 5 . Moreover, comparing the 13 C‐NMR spectral data of 5 with those of a reference compound, gregatin B, we found that the carbon signals of compound 5 in the C2, C3, C13, and C14 were almost identical to those of gregatin B. Hence, the C‐3 was undoubtedly substituted by a carboxylic acid unit on the basis of the previously mentioned evidence.…”

Pulvinulin A, Graminin C, and cis-Gregatin B – New Natural Furanones from Pulvinula sp. 11120, a Fungal Endophyte of Cupressus arizonica

“…Comparison of the 1 H and 13 C NMR data of the metabolite 3 , [α] D 25 +168, with those reported for synthetic cis -gregatin B [11] suggested that they are identical with each other. The absolute configuration at the only chiral center (C-5) in synthetic 3 was established as R based on the absolute configuration of the starting materials used for its synthesis, but its [α] D value has not been determined due to the lack of sufficient material [11].…”

“…Despite its simplicity, the central core of these metabolites has undergone several structural revisions over the past three decades. The core structure, 3-acyl-4-methoxyfuran-2( 3H )-one, the first proposed for these metabolites [8,9], was later revised to 4-acyl-3-methoxyfuran-3( 2H )-one [10], and finally to the currently accepted 4-(methoxycarbonyl)furan-3( 2H )-one [11]. Several fungal-derived furanones have been reported to have phytotoxic [12], antibacterial and antifungal activities [9] and implicated as the causal agents of stripe disease of wheat [12] and brown stem rot of adzuki beans [9].…”

“…The absolute configuration at the only chiral center (C-5) in synthetic 3 was established as R based on the absolute configuration of the starting materials used for its synthesis, but its [α] D value has not been determined due to the lack of sufficient material [11]. Catalytic hydrogenation of 3 afforded its new derivative, 1'(2'),3'(4')- tetrahydro-gregatin B ( 9 ) (Figure 3), [α] D 25 −57.…”

Secondary metabolites from the endolichenic fungusOphiosphaerella korrae

“…9 Herein, we continued our chemical investigation on the three cytotoxic fractions G, I and L (which were active against the A549 cells with IC 50 values of 13.36, 23.63 and 25.28 mg mL À1 , respectively). Six new metabolites (1-5 and 10), together with nine known metabolites including four aromatic polyketides (6)(7)(8)(9) and ve perylenequinones (11)(12)(13)(14)(15), were obtained ( Fig. 1).…”