Synthesis Of Bicyclic Heterocycles Containing An N-O Bond And Marine Butenolides

Natural products,the molecules originated from Nature,mostly exhibit cytotoxic,antibacterial,and other biological activities.They are of important values to the living and manufacturing of mankind.This thesis deals with synthesis of marine butenolides and the bicyclic heterocycles possessing an N-O bond.Chapter 1 mainly introduces the various types of natural products,total synthesis, and the related topics.The N-O bond containing heterocycles are first discussed, covering not only their structural diversity and versatile synthetic methodologies,but also the examples of total synthesis involving the N-O bond containing heterocycles as the intermediates.A key focus of this thesis is the total synthesis of marine butenolides,and their isolation and structural characterization are described.Presented in Chapter 2 are the experimental details on synthesis of the bicyclic heterocycles bearing an N-O bond.The results include preparation of the substrates, optimization of the conditions for the microwave-assisted intramolecular Diels-Alder (IMDA) cycloaddition,characterization of the adduct structures,and influence of Cl-, C5-,and C10-appendage(s) on the stereoselectivity of the IMDA cycloaddition.The results of this work provide the basis for revision of the incorrect conclusion found in the literature about the high stereoselectivity of IMDA of the hydroxamate-tethered 1,3,9-decatrienes.The latter actually share similar stereoselectivity with the parent 1,3,9-decatrienes.It was found that the hydroxamate-tethered 1,3,9-decatrienes underwent the unknown 1,5-rearrangement,accounting for the observed additional cycloadducts.Furthermore,X-ray single crystal structural analyses were performed for three adducts,whose structures and relative stereochemistry were confirmed.Total synthesis and stereochemical assignment of the butenolides-derived chiral alcohols and ketones are the major effort of this thesis research.Chapter 3 first briefs on the known synthesis of the diastereomeric butenolide alcohols.It is followed by the "three module coupling" strategy applied in this work according to 1,3-dithiane bisalkylation.Two diastereomeric butenolide alcohols possessing a C10-C11 syn-aldol subunit were synthesized,including new preparation of the C3-C7 alkyl iodide in an optically pure form.The target molecules were obtained in high diastereomeric ratios,and this work produced the optical rotation data for the two butenolide alcohols and the corresponding butenolide ketones,enabling assignment of the absolute configurations of the naturally occurring butenolides.The experimental section compiles the main synthetic procedures,the characterization data for the key compounds,and the cited references.Copies of the original ¹H and ¹³C NMR spectra and the X-ray single crystal structural analysis data are found in the Appendix.