A Solid-Phase Synthesis of 3,4-Dihydro-1H-2,1-benzothiazin-4-one 2,2-Dioxide Derivatives
- 주제(키워드) Solid-Phase Synthesis
- 발행기관 서강대학교 일반대학원
- 지도교수 이덕형
- 발행년도 2009
- 학위수여년월 2009. 8
- 학위명 석사
- 학과 일반대학원 화학과
- 실제URI http://www.dcollection.net/handler/sogang/000000045408
- 본문언어 한국어
- 저작권 서강대학교의 논문은 저작권에 의해 보호받습니다
초록/요약
Sulfonamides are prevalent structural features of many pharmaceutical agents. The corresponding cyclic sulfonamides have therefore been pursued as potential pharmaceutical scaffolds in their own right. Among the variety of cyclic sulfonamides, 3,4-dihydro-1H-2,1-benzothiazin-4-one 2,2-dioxide derivatives have been far less explored compared to the analogous, positionally isomeric 3,4-dihydro-2H-1,2-benzothiazin-4-one 1,1-dioxide derivatives, among which Meloxicam and Piroxicam are commercially successful NSAIDs (nonsteroidal anti-inflammatory drugs). Although some 1H-2,1-benzothiazine 2,2-dioxide derivatives were recently reported to have biological activities such as IL-8 receptor antagonistic, 5-HT receptor antagonistic, factor Xa inhibitory, and reverse transcriptase (RT) inhibitory activities, the reports have been rare on the biological relevance of the corresponding 4-oxo derivatives as core structure. Utilizing polymer-bound anthranilic acid derivatives, we were able to obtain 3,4-dihydro-1H-2,1-benzothiazine-4-one 2,2-dioxide derivatives through N-methanesulfonylation by use of sulfonyl chloride, sulfonic acid, or sodium sulfonate, N-alkylation under Mitsunobu condition, and the cyclative cleavage in 10-52% five-step overall isolated yields and 92-99% purities from Wang resin. The reactions on solid phase were monitored by on-bead ATR-FTIR spectroscopic method and checked by help of solution-phase model experiments.
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