Biomimetic Total Synthesis of Angiopterlactone B and Other Potential Natural Products

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.

Unusual Epimerization in Styryllactones: Synthesis of (−)-5-Hydroxygoniothalamin, (−)-5-Acetylgoniothalamin, and O-TBS-Goniopypyrone

“…To investigate this unexpected epimerization reaction, we prepared various substituted 5,6-dihydropyran-2-ones by following literature procedures. 15 We reacted various 5,6-dihydropyran-2-one systems under the same reaction conditions mentioned above (Scheme S1, see the Supporting Information). However, we did not observe any epimerized product, and only the TBS-deprotected products were obtained.…”

Formal Synthesis of Angiopterlactone B via Enantioselective Reduction of Ketone with Daucus Carota Root

“…Synthesis of angiopterlactone B commenced with intermolecular oxa-Michel addition of (S,S)-osmundalactone 7 and 5membered lactone 8 whose framework based on (4S,5S)-ethyl 5-(tert-butyldimethylsilyloxy)-hydroxyhex-2-ynoate 9. [3] To introduce 6S,5S stereocenter in 2 herein we initiated this synthesis with chiral substrate (-)-ethyl L-lactate 11. Ester 11 reduced to aldehyde with DIBALÀH in DCM at À78 0 C after silyl protection [4] with TBSCl.…”

“…Angiopterlactone A 1 could be biosynthetic precursor of angiopterlactone B 2 which have unique structural features i.e tricyclic ring network pattern including two lactones, ether linkage, and seven adjacent stereocenters. Not long ago when our synthesis was in progress, the total syntheis has been reported by group of Bhattacharya applying intermolecular oxa‐ Michael addition of lactone 7 and 8 . We envisioned the same protocol of oxa‐Michael addition for the synthesis of 2 .…”

“…Not long ago when our synthesis was in progress, the total syntheis has been reported by group of Bhattacharya applying intermolecular oxa-Michael addition of lactone 7 and 8. [3] We envisioned the same protocol of oxa-Michael addition for the synthesis of 2. To procure six-membered and five-membered lactone, we traced back our synthesis starting from ethyl l-lactate and ethyl propiolate which afforded propargylic ketone carbon skeleton, carbonyl functionality of ketone 14 was reduced using biocatalyst.…”

Synthesis of 6,12-Disubstituted Methanodibenzo[b,f][1,5]dioxocins: Pyrrolidine Catalyzed Self-Condensation of 2′-Hydroxyacetophenones

“…Heterocyclic compounds possess fascinating complex structural architecture and are key structural motifs in an array of biologically active natural products and pharmaceutically active compounds [1], which drives the development of improved and new synthetic methodologies [2,3,4,5,6,7,8,9]. In recent years, cascade reactions [10,11,12,13,14,15,16] and bio-inspired technologies [17,18,19,20,21,22,23] have been employed to access structural complexity in compounds of biological importance.…”