Chemistry PhD Student, The University of Edinburgh, Lawrence Group
(+)-Angiopterlactone B is a structurally complex bis-lactone metabolite, which was isolated from the rhizome of Angiopteris caudatiformis by Zou and co-workers in 2009. The structural complexity of this metabolite, as well as the biological activities reported for the extracts of Angiopteris plants, make this compound of significant interest to synthetic chemists.
Synthetic biomimetic investigations have successfully resulted in a four-step total synthesis of (−)-angiopterlactone B, starting from commercially available 2-acetylfuran. The structure, including absolute stereochemistry, was confirmed by X-ray crystallography. Particularly noteworthy is the final biomimetic dimerisation, which forms three new bonds, two new rings and three new contiguous stereogenic centres in a single step. This synthesis exemplifies how biosynthetic considerations can lead to the development of domino reaction sequences, which rapidly generate molecular complexity.
Abstract: An enantioselective total synthesis of (-)-angiopterlactone B has been accomplished in four steps. The synthesis features a proposed biomimetic domino ring-contraction/oxa-Michael/Michael dimerization sequence, forming three new bonds, two new rings, and three new contiguous stereogenic centers in a single step. It has been determined that the originally proposed absolute configuration of natural (+)-angiopterlactone B needs revision. This reveals that angiopteroside, a known glycoside natural product, is the likely biosynthetic precursor to (+)-angiopterlactone B.
Pub.: 21 Apr '17, Pinned: 07 Jun '17
Abstract: A one-pot biomimetic synthesis of (-)-angiopterlactone B and its enantiomer (+)-angiopterlactone B has been accomplished via TBAF-catalyzed tandem ring contraction followed by oxa-Michael/Michael addition sequence. Comparison of specific optical rotations, absolute configurations, and CD spectra of natural, synthesized (-)-angiopterlactone B and (+)-angiopterlactone B unequivocally proves that the isolated angiopterlactone B must be levorotatory. Synthesis of hitherto undiscovered natural products 18 and 20 and analogues of angiopterlactone B demonstrate the versatility of this method.
Pub.: 15 Jun '17, Pinned: 04 Jul '17
Abstract: A series of spirooxindole tetrahydrofuran derivatives 3 were obtained in moderate to good yields via oxindole derivatives 1 and β-arylacrylonitrile derivatives 2via base-mediated cascade [3 + 2] double Michael reactions under mild conditions and the application of this method in the synthesis of bioactive analogues, such as functionalized spirooxindole octahydrofuro[3,4-c]pyridine derivatives 4 which contain two new heterocyclic rings and two quaternary carbon centers, has also been developed. Subsequently, antifungal activities of all of the synthesized compounds were evaluated against five phytopathogenic fungi (Rhizoctonia solani, Fusarium semitectum, Alternaria solani, Valsa mali and Fusarium graminearum) using the mycelium growth rate method. The preliminary results showed that the spirooxindole octahydrofuro[3,4-c]pyridine derivative 4 showed higher growth inhibition of Valsa mali and Fusarium graminearum, than spirooxindole tetrahydrofuran derivatives 3. For example, spirooxindole octahydrofuro[3,4-c]pyridine derivative 4ab, having a bromine atom at the meta position of the benzene ring, was the best compound in inhibiting F. g. with an IC50 value of 3.31, in particular with inhibition of 4ab on F. g. being similar to that of the control cycloheximide (IC50 = 3.3 μg mL(-1)).
Pub.: 31 Mar '15, Pinned: 15 Jun '17
Abstract: [reaction: see text] The asymmetric synthesis of pentacyclic derivatives was achieved in a single step starting from enantiopure [(S)R]-[(p-tolylsulfinyl)methyl]-p-quinols or the nitrogen analogue, through a domino sequence involving four conjugate additions in excellent yields. Eight new stereogenic centers were created in one step and in a highly diastereoselective manner.
Pub.: 05 Jul '03, Pinned: 15 Jun '17
Abstract: Chemoenzymatic and stereoselective total syntheses of the non-natural enantiomeric forms of the recently isolated protoilludane natural products 8-deoxydihydrotsugicoline (1) and radudiol (2) (viz. ent-1 and ent-2, respectively) are reported. The key steps involve the Diels–Alder cycloaddition of cyclopent-2-en-1-one to the acetonide derived from enantiomerically pure and enzymatically derived cis-1,2-dihydrocatechol 3, elaboration of the resulting adduct to the tricyclic ketone 12, and a photochemically promoted rearrangement of this last compound to the octahydro-1H-cyclobuta[e]indenone 13.
Pub.: 03 Feb '16, Pinned: 15 Jun '17
Abstract: Angiopterlactones A (1) and B (2), two unique lactones, and three known lactones, osmundalactone (3), osmundalin (4), and 3,5-dihydroxy-gamma-caprolactone (5), have been isolated from the rhizome of Angiopteris caudatiformis. The structures of 1 and 2 were determined by NMR and MS methods, and the structure of 2 was confirmed by X-ray crystallography. The absolute configurations of 1 and 2 were assigned by application of the CD excitation chirality method and the modified Mosher's method. Compound 1 was slightly cytotoxic against HeLa cells, with an IC(50) value of 68.8 microM, and compounds 3 and 4 showed moderate insect antifeeding activity against Plutella xylostella and Heliothis virescens.
Pub.: 18 Apr '09, Pinned: 07 Jun '17
Abstract: The total synthesis of the racemic natural products (±)-incarviditone and (±)-incarvilleatone has been accomplished in three steps via biomimetic dimerization of (±)-rengyolone. Homochiral dimerization of (±)-rengyolone affords (±)-incarviditone through a domino oxa-Michael/Michael sequence. Heterochiral dimerization, involving a domino oxa-Michael/Michael/aldol reaction sequence, affords (±)-incarvilleatone. Single-crystal X-ray analysis of a derivative of (±)-incarviditone has resulted in revision of the originally proposed structure.
Pub.: 31 Aug '12, Pinned: 07 Jun '17