Studies On The Syntheses Of Analogs Of Shuangkangsu-an Anti-virus Principle Of JinYinHua

1. Total syntheses of Shuangkangsu and its optically active analogs.Shuangkangsu, a novel chiral cyclic peroxide, was firstly isolated by our group from Chinese traditional medicine-Jinyinhua which was used to treat with rheum. It showed obvious inhibition of flu virus in chicken embryo and of respiratory syncytial virus in cells.The structure of Shuangkangsu with optical activity was determined by ¹HNMR, ¹³CNMR, and MS spectral data. The absolute configurations of C-1 and C-4 were proposed to 1S, 4S by its CD spectrum. The purpose of this study was, therefore, to find new method for the formation of peroxide and glycosyl method for hydroxyl of Shuangkangsu, and to study the anti-virus activity and structure-activity relationship, as well as to prove the absolute configuration of C-1 and C-4 of Shuangkangsu,. We studied the total syntheses of Shuangkangsu and its analogs.(1). The method for the formation of peroxide in the skeleton of Shuangkangsu, which is intramolecular addition of H₂O₂ to the 1, 2-dialdehyde was established. This method expanded the applied scope of the methods reported in literature. The two cyclic peroxides 2 and 11 were synthesized by the method.(2). The optically active analogs of Shuangkangsu 48c and 48d were successfully synthesized from substrate 2. The glycosyl method for hydroxyl of substrate 2 was developed: By treated with NIS and AgOTf, the alkyl thioglycoside donor reacted with the acceptor substrate 2 to afford orthoester 45 which was rearranged to compound 48 catalyzed by BF₃.Et₂O. Optical pure isomers 48a and 48b were obtained by preparative HPLC. By comparison the CD spectra of compound 48a and 48b with those of compounds 30 and 31, the absolute configuration of 48a and 48b were determined to (1R, 4R) and (IS, 4S), respectively. 48c and 48d were obtained by removing the acetyl group in compounds 48a and 48b, respectively.(3). The relative configuration of this type of cyclic peroxides were determined by the X-ray diffraction analysis of compounds 30 derived from the substrate 2 and (-)-menthol. In this type of cyclic peroxides, the relative configurations of substitutes at C-1 and C-4 were trans. The absolute configuration of Shuangkangsu was determined to (IS, 4S) by comparison its CD spectrum with CD spectra of compounds 30 and 31.(4). The mechanisms of the decomposition of the peroxides catalysed by alkali were firstly discussed based on the decomposition products of compounds 2, 23, 26 and so on..(5). Three routes were designed for the synthesis of the key intermediate 3, two of which were failed and the third is in progress.(6). Peroxides 23, 24, 25, 26, 30, 31 showed no obvious anti-tumor activity.2. Total syntheses and biological evaluation of natural product A1 and its epimer A2(R)-4-Phenyl -2-O-[β-D-xylopyranosyl (1→6)-β-D-glucopyranosyl] butane (AI) was a new natural product isolated from Rhododendron athopogonosides Maxim by our group. The absolute configuration of C-2 of A1 was grossly determined to R. However, it was disturbing to observe that [α]_D value of aglycone was noticeably different from the reported data. In order to confirm the absolute configuration of A1 and master the skill of glycosyl method, A1 and its epimer A2 were synthesized.(1). A1 and its epimer A2 were firstly synthesized by 11-steps reaction from starting material 4-phenyl-2-butanone. The absolute configuration of the A1 was determined. In conclusion, the glycosyl donors should be selected according to the properties of hydroxyl acceptors.(2). Compounds A1, A2, 93 and 94 showed no obvious activities against human A549, BEL7402, BGC823, HCT-8 and A2780 cell lines.88 compounds were synthesized in the above-mentioned dissertations, in which 42 compounds (including 28 optical pure compounds) were the new ones with no report before.