Synthetic Applications of Sulfur-Substituted Indolizidines and Quinolizidines

Chou, Shang‐Shing P.; Chung, Yi-Ching; Chen, Po–An; Chiang, Shan-Lun; Wu, Chien‐Jung

doi:10.1021/jo102092b

Cited by 41 publications

(11 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Related cermizine alkaloids have attracted the attention of several laboratories. 2 To date, one elegant eighteen-step total synthesis of 1 has been reported by Takayama and co-workers. 3 Herein, we report an efficient, enantioselective synthesis of cermizine D, which exploits the use of a common intermediate strategy to access two of the three piperidine rings.…”

mentioning

confidence: 99%

Expedient Enantioselective Synthesis of Cermizine D

2012

View full text Add to dashboard Cite

An efficient enantioselective synthesis of cermizine D has been developed that exploits the use of a common intermediate to access over 85% of the carbon backbone. Key steps include an organocatalyzed heteroatom Michael addition, a diastereoselective alkylation with α-iodomethyl phenyl sulfide, a conjugate addition to a vinyl sulfone species and a sulfone coupling / desulfurization sequence to join the two major subunits.

show abstract

mentioning

confidence: 99%

Expedient Enantioselective Synthesis of Cermizine D

2012

View full text Add to dashboard Cite

show abstract

“…Our previous study demonstrated that a new aza-Diels-Alder reaction of thio-substituted 3-sulfolenes with p-toluenesulfonyl isocyanate (PTSI) can synthesize several sulfur-substituted piperidine derivatives [11]. Based on this method, a series of quinolizinones and pyridones were synthesized in this study to evaluate their biological function in anti-inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

“…1A [11], [12], [13], [14], [15] and their name of these chemical compounds were listed on Table 1. Lipopolysaccharides (LPS, Escherichia Coli 0111:B4) were purchased from Sigma-Aldrich (Saint Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The biological function and underlying mechanisms of these compounds against inflammation remain unknown. We synthesized a series of quinolizinone and pyridone derivatives based on the previous methods [11] and evaluated their biological function in anti-inflammatory responses. This study investigated the underlying effects and mechanisms of these newly synthesized compounds in anti-inflammatory responses stimulated by lipopolysaccharide in a murine macrophage cell line and animal model.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

FJU-C4, a New 2-Pyridone Compound, Attenuates Lipopolysaccharide-Induced Systemic Inflammation via p38MAPK and NF-κB in Mice

et al. 2013

Self Cite

View full text Add to dashboard Cite

Despite advances in antibiotic therapy and intensive care, the mortality caused by systemic inflammatory response syndrome and severe sepsis remains high. The use of anti-inflammatory agents to attenuate inflammatory response during acute systemic inflammatory reactions may improve survival rates. Here we show that a newly synthesized 2-pyridone compound (FJU-C4) can suppress the expression of late inflammatory mediators such as iNOS and COX-2 in murine macrophages. The pro-inflammatory cytokines, including TNFα, IL-1β, and IL-6, were dose-dependently suppressed by FJU-C4 both in mRNA and protein levels. In addition, the expression of TNFα was inhibited from as early as 2 hours after exposure to LPS stimulation. The production of mature pro-inflammatory cytokines was also suppressed by pretreatment with FJU-C4 in either cell culture medium or mice serum when stimulated by LPS. FJU-C4 prolongs mouse survival and prevents mouse death from LPS-induced systemic inflammation when the dose of FJU-C4 is over 5 mg/kg. The activities of ERK, JNK, and p38MAPK were induced by LPS stimulation on murine macrophage cell line, but only p38MAPK signaling was dramatically suppressed by pretreatment with the FJU-C4 compound in a dose-dependent manner. NF-κB activation also was suppressed by FJU-C4 compound. These findings suggest that the FJU-C4 compound may act as a promising therapeutic agent against inflammatory diseases by inhibiting the p38MAPK and NF-κB signaling pathway.

show abstract

“…Imino-Diels-Alder reactions are very useful for the synthesis of tetrahydropyridines [17][18][19]. We have previously developed a new imino-Diels-Alder reaction of thio-substituted 3-sulfolenes with p-toluenesulfonyl isocyanate (PTSI) to synthesize piperidine derivatives [20,21], and have used this method to prepare some indolizidines and quinolizidines [22][23][24][25][26][27][28][29][30][31][32]. We have recently reported the use of cross metathesis (CM) to transform the terminal alkenes 1a-c into the α,β-unsaturated esters 2a-c, and after detosylation the resulting amides 3a-c…”

Section: Introductionmentioning

confidence: 99%

Studies toward the First Stereoselective Total Synthesis of (±)-Quinolizidine 195C and Other Transformations

Chou

Huang

2013

Molecules

View full text Add to dashboard Cite

Abstract:Starting from a thio-substituted 4-quinolizidinone, a series of C-6 alkylated derivatives with a trans C-6, C-9a relationship was synthesized. Further transformations led to the first stereoselective total synthesis of the structure proposed for (±)-quinolizidine 195C, the major alkaloid isolated from the skin extracts of the Madagascan frog Mantella betsileo. Since the spectral data of the synthetic and natural products differed significantly, the true structure of (±)-quinolizidine 195C remains uncertain.

show abstract

Synthetic Applications of Sulfur-Substituted Indolizidines and Quinolizidines

Cited by 41 publications

References 26 publications

Expedient Enantioselective Synthesis of Cermizine D

Expedient Enantioselective Synthesis of Cermizine D

FJU-C4, a New 2-Pyridone Compound, Attenuates Lipopolysaccharide-Induced Systemic Inflammation via p38MAPK and NF-κB in Mice

Studies toward the First Stereoselective Total Synthesis of (±)-Quinolizidine 195C and Other Transformations

Contact Info

Product

Resources

About