Abstract
This thesis consists of two part, the first part deals with the total synthesis of (±)-pterosin A, (R)-pterosin A, (S)-pterosin D and (2S,3S)-pterosin C. The synthesis of (±)-pterosin A started from the reaction of 2-bromo-1,3-dimethylbenzene 1 with -chloropropionyl chloride by using Friedel-Crafts acylation that followed by Nazarov cyclization to afford indanone 29. Indanone 29 is converted to -keto ester 50 by ethoxycarbonylation and methylation. The use of Suzuki coupling reaction is a key step in the synthesis to construct the C6-side chian and then after some functional group transformation -keto ester 50 is converted to (±)-pterosin A. In this synthesis, (±)-pterosin A was accomplished in 9 steps and 10% overall yield. In the synthesis of (R)-pterosin A, PLE (porcine liver esterase) is used to proceed desymmetrization of diester 90 to afford known chiral compound 91. compound 91 is converted to vinyl iodide 95 followed by Stille coupling to afford diene 97. Diene 97 is converted to diene-ynone which could be directly subjected to intramolecular Diels-Alder reaction/aromatization to give (R)-pterosin A. By using the same strategy in the synthesis of (R)-pterosin A, (2S,3S)-pterosin C is synthesized form the known compound aldehyde 109 of Evans’ aldol reaction to give diene 111 with suitable skeleton and chiral center at C2 and C3 of pterosin C. Then, diene 111 was transformed into diene-ynone 113 followed by intramolecular Diels-Alder reaction/aromatization, and the removal protecting groups to afford (2S,3S)-pterosin C. The synthesis of (S)-pterosin D is started form commercially available D-(-)-pantolactone (118). D-(-)-pantolactone (118) is converted to vinyl iodide 125 that possess required functional group and chiral center at C2 and C3 of pterosin D. Vinyl iodide 125 is converted to diene 127 by Stille coupling reaction. Diene 127 is converted to diene-ynone intermediate using a similar synthetic sequence that is reported in section 3. Diene-ynone undergoes intramolecular Diels-Alder reaction/aromatization followed by removal protecting TBS groups to afford (S)-pterosin D. The second part of this thesis deals with the synthesis of Entecavir. In this part, intemediates were (-)-195 and (-)-204 from epoxy alcohol 193. Cyclization of either intermediate by NHK cyclization or radical cyclization will give triol intermediate as the precursor for the synthesis of Entecavir.