Shuangjie Lin

Stereoselective total synthesis of (–)-(6S,2′R)-cryptocaryalactone

Abstract We described a novel stereoselective total synthesis of (–)-(6S,2′R)-cryptocaryalactone, a natural product containing syn/anti-6,8-diol/5,6-dihydro-2H-pyran-2-one unit. The approach, which characterised a highly diastereoselective chelation-controlled Mukaiyama aldol reaction of a benzyl-protected aldehyde and a Yamaguchi lactonisation of a δ-hydroxy-trans-α,β-unsaturated carboxylic acid, is an alternative synthetic strategy towards cryptocaryalactones.

Asymmetric Total Synthesis of Ieodomycin B

Ieodomycin B, which shows in vitro antimicrobial activity, was isolated from a marine Bacillus species. A novel asymmetric total synthetic approach to ieodomycin B using commercially available geraniol was achieved. The approach involves the generation of 1,3-trans-dihydroxyl at C-3 and C-5 positions via a Crimmins-modified Evans aldol reaction and a chelation-controlled Mukaiyama aldol reaction of a p-methoxybenzyl-protected aldehyde, as well as the generation of a lactone ring in a deprotection–lactonization one-pot reaction.

Synthetic study towards (+)-vertine and (+)-lythrine synthesis of the intermediate of benzyl-2-(1-methoxy-1,3-dioxobutan-2-yl)piperidine-1-carboxylate

Synthetic study of the intermediate of (+) vertine and (+) lythrine, benzyl – 2 ( 1 – methoxy 1,3dioxobutan -2 –yl ) piperidine -1carboxylate was described, which included protection, reduction and addition of silyl enol ether. Introduction In 1962, a series of phenylquinolizidinine alkaloids were isolated from a flowering plant in the Lythraceae family by Ferris and co-workers, which was named Decodon verticillatus, commonly known as water willow or swamp loosestrife and endemic to wetlands in the eastern half of the United States. Vertine and lythrine (shown in Figure 1) are two of the most studied alkaloids of this family. Vertine and lythrine was explored to possess a wide range of biological activities such as antiinflammatory, sedative, and antispasmodic actions. Till now, Laetitia Chausset-Boissarie and co-workers reported the synthesis of (±)-vertine and they also described the synthesis of (+)-vertine and the first total synthesis of (+)-lythrine [1, 2]. Herein, we described the intermediate of vertine and lythrine, benzyl-2-(1-methoxy-1,3-dioxobutan-2-yl)piperidine-1-carboxylate.

Synthetic Study towards Entecavir

A synthetic design of Entecavir was described, and the intermediate, (S)-N-methoxy -3-((4-methoxybenzyl)oxy)-N-methylpent-4-enamide, was synthesized using acrylaldehyde as the starting material, which was obtained via an Evans Aldol reaction, Weinreb amide formation, and a PMB protection. Introduction Hepatitis B virus (HBV) represents one of the most prevalent viral diseases in the world and is known to be a cause of serious liver disorders. It is reported that more than 400 million people have been chronically infected and there is a continuing need for new therapies for individuals infected with HBV. Entecavir (BMS-200475, 1) (Fig. 1) is a carbocyclic guanosine nucleoside analog with potent selectivity against hepatitis B virus which was approved under the trade name Baraclude in March 2005 by the US Food and Drug Administration for the treatment of chronic HBV infection in adults. Entecavir inhibits DNA synthesis in HBV infected cells in three steps: the priming of the polymerase, the reverse transcription of the pregenomic messenger RNA and the synthesis of the positive strand of HBV DNA. Entecavir is also effected to lamivudineand adefovir-resistant HBV strains. Figure 1. The structure of Entecavir As Entecavir’s remarkable potency, resistance, and safety profile, a great deal of synthetic effort has been devoted to the enantiospecific syntheses of Entecavir, among which most reported syntheses employ five-membered carbocyclic compounds as the starting material. In our study, we would describe our synthetic analysis towards Entecavir using acrylaldehyde as the starting material to construct the protected five member ring Entecavir 1 and our present work of the synthesis towards Entecavir. Our retrosynthetic route is outlined in Scheme 2. International Conference on Advances in Energy, Environment and Chemical Engineering (AEECE-2015)

Synthetic Study towards (±)-Vertine and (±)-Lythrine

A synthetic design of (±)vertine and (±)-lythrine was described, and the intermediate, N-protected 2-methoxypiperidine, was synthesized, which contains a protection, reduction and etherification. Introduction In 1962, Ferris and co-workers had isolated phenylquinolizidinine alkaloids from a flowering plant in the Lythraceae family, Decodon verticillatus, which was commonly existed in United States. Later, Schwarting and co-workers examined Heimia salicifolia and other Heimia species. Vertine and Lythrine (Figure 1.) are two of the most studied alkaloids of this family. They had a wide range of biological activities such as sedative, antispasmodic and anti-inflammatory activities. They also played an important role in regulation of glucose level in blood and lower blood pressure. It has a strained 12-membered ring with three stereogenic centers, two of which are part of the macrocycle and an induced chiral biaryl axis. All of these synthetical challenges attracted scientists’ interest. In the 2012, Laetitia Chausset-Boissarie and co-workers described the synthesis of (+)-vertine and the first total synthesis of (+)-lythrine. Figure 1. Structure of Vertine and Lythrine Our retrosynthetic analysis of Vertine and Lythrine is displayed in Scheme 1. International Conference on Advances in Energy, Environment and Chemical Engineering (AEECE-2015)