Total Synthesis Of Several Natural Dracaenones And Streptanoate

As secondary metabolites produced by organisms,natural products are numerous in variety,large in quantity and novel in molecular structure,which can be used as precursors for functional compounds such as medicines and pesticides.As a key topic in organic chemistry,the total synthesis of natural products is aimed at obtaining targeted natural products,providing a large number of research materials,determining the structure and absolute configuration of chiral compounds,and developing new types of organic reactions and catalysts,etc.Natural products are mainly derived from plants and microorganisms.In this article,a series of plant-derived dracaenones and microorganism-derived Streptanoate were selected for total synthesis.We completed the first total synthesis of four natural dracaenones,two enantiomers and two dracaenones’analogues,then their absolute configurations were determined,which were the first chiral level-based total synthesis of the dracaenone family.At the same time,a natural product of benzodihydropyran was synthesized,and a good method for synthesizing the dracaenones was found.Finally,the natural product Streptanoate derived from the microorganism of Streptomyces was total synthesized and its absolute configuration was determined.All of the new compounds synthesized herein were characterized by¹H NMR,¹³C NMR,IR,HR-MS,OR,and melting point（partial compound）.For the establishment of the spiro-bridged ring skeletons in dracaenones,a series of oxidative coupling reactions using benzodihydropyrans as precursors and bis（trifluoroacetic acid）iodobenzene（PIFA）as oxidants were conducted,which gave an efficient method for synthesizing dracaenones—PIFA/Phosphotungstic acid oxidative coupling method.For natural 10,11-dihydroxydracaenone C（3-1）,the chiral Evans auxiliary group was used as raw material to obtain a single configuration of compound 3-5 by classical Evans Aldol condensation under TiCl₄ condition.The C-7 and C-8 chiral centers were successfully constructed,and then the auxiliary group was removed.After cyclization and reduction,the C-8 hydroxyl group was removed to obtain a single configuration of the benzodihydropyran 3-18.Oxidative coupling was carried out by PIFA/PTA condition,and compound 3-1 and its enantiomer ent-3-1 were obtained,the absolute configuration of the natural product determined as（7S,12bR）.The first total synthesis of the natural product（S）-3-2 was also completed.We found that the NMR and specific rotation solvents of the natural product 3-1 reported in the literature were incorrect which should be DMSO.For natural 10-hydroxy-11-methoxydracaenone（4-1）,the chiral Evans auxiliary group was used as the raw material to obtain compound 4-5 with a single configuration by classical Evans Aldol condensation under TiCl₄ condition,with the C-7 and C-8 chiral centers successfully constructed.The hydroxyl group of C-8 was reduced,and the precursor compound 4-2 was obtained.Compound 4-1 and its enantiomer ent-4-1 were synthesized by different protection of the hydroxyl group in compound 4-2,and the absolute configuration of the natural product was determined as（7S,12bR）.The optical rotation of 4-1 in different concentrations of methanol was studied to explain the difference in specific optical rotation reported by Cordell and Li Ning et al.（the opposite sign,the numerical difference is very large）.For natural 7,10,11-trihydroxydracaenone（5-1）,the chiral aziridine derivative was used to obtain a chiral compound 5-3a by the Davis asymmetric oxidation.The benzodihydropyran precursor compound was obtained by reduction.Under the PIFA/PTA condition,compound ent-5-1 was synthesized for the first time.After comparing ¹H NMR,¹³C NMR and specific optical rotation data with the natural product,the absolute configuration of the natural product was determined as（7R,12bR）.Using a similar method,the total synthesis of Epicaesalpin J（5-2）was completed for the first time.The stereo structure of compound 5-2 was confirmed by¹H and ¹³C NMR,COSY,NOESY,DEPT,HSQC and HMBC.We have corrected the characterization results of chemical shifts of natural products at C-8 and C-12a in the literature and the absolute configuration of Epicaesalpin J was defined as（7R,12bS,13R）.For natural product Streptanoate with antitumor activity derived from Streptomyces microorganisms,two chiral isomers of compound 6-1 were synthesized according to the structure reported in the literature.The structural characterization studies proved that the structure of Streptanoate reported in the literature was wrong.Four chiral isomers of the two possible structures 6-9 and 6-10 of the natural product were speculated and synthesized based on literature data.By"titrating"the NMR sample solution,when the ratio of the solvent DMSO to CDCl₃ was 1:1,the NMR data of compound（2R,2’R）-6-10 was consistent with the data of natural product Streptanoate.Combined with the optical rotation data,it was determined that the structure of the natural product Streptanoate should be（2R,2’R）-6-10.