Constituents of <i>Nauclea</i><i>diderrichii</i>. Part VII. Synthesis of nauclederine, naucleonine, and naucleonidine; spectroscopic evidence for the structures of 3α-dihydrocadambine and two other constituents

McLean, Stewart; Dmitrienko, Gary I.; Szakolcai, Akos

doi:10.1139/v76-179

Cited by 15 publications

(8 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 1 H-NMR data of cadamine ( 2 ) was reported previously based on cadamine acetate [ 7 ] whereas 3 were first isolated from Nauclea diderrichi [ 10 ]. We herein report the 13 C-NMR data for both compounds which has not been reported yet [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. In view of that, complete assignments were established through various NMR measurements; DEPT, HMQC, HMBC and NOESY spectra.…”

Section: Resultsmentioning

confidence: 99%

“…In continuation of our research on plants from the Rubiaceae family [ 6 ], we have embarked a study on the CH 2 Cl 2 extract of the plant Ochreinauclea maingayii . The present study has led to the isolation of a new indole alkaloid, neonaucline ( 1 ) together with cadamine ( 2 ) [ 7 , 8 , 9 ], naucledine ( 3 ) [ 10 , 11 , 12 , 13 ], harmane [ 14 , 15 ], blumenol A [ 16 ], bezamide, and cinnamide.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neonaucline, a New Indole Alkaloid from the Leaves of Ochreinauclea maingayii (Hook. f.) Ridsd. (Rubiaceae)

Osman

Awang

et al. 2011

Molecules

View full text Add to dashboard Cite

A new indole alkaloid; neonaucline (1), along with six known compounds–Cadamine (2), naucledine (3), harmane, benzamide, cinnamide and blumenol A–were isolated from the leaves of Ochreinauclea maingayii (Rubiaceae). In addition to that of compound 1, 13C-NMR data of cadamine (2) and naucledine (3) were also reported. Structural elucidations of these alkaloids were performed using spectroscopic methods especially 1D- and 2D-NMR, IR, UV and LCMS-IT-TOF. The excellent vasorelaxant activity on isolated rat aorta was observed for the alkaloids 1–3 after injection of each sample at 1 × 10−5 M.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neonaucline, a New Indole Alkaloid from the Leaves of Ochreinauclea maingayii (Hook. f.) Ridsd. (Rubiaceae)

Osman

Awang

et al. 2011

Molecules

View full text Add to dashboard Cite

show abstract

“…The title compound was prepared in the same manner as described for 9a using 2-(3-pyridyl)oxirane 21) ,6.10;N,13.57;Cl,8.59. Found: C,63.76;H,5.90;N,13.68;Cl,8.46.…”

Section: -(2-{[2-hydroxy-2-(3-pyridyl)ethyl]amino}ethyl)-2-(2-pyridylmentioning

confidence: 99%

Synthesis and Evaluation of Novel Phenylethanolamine Derivatives containing Acetanilides as Potent and Selective .BETA.3-Adrenergic Receptor Agonists

Maruyama

Onda

Hayakawa

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

A major increase in the prevalence of obesity and non-insulin dependent (type II) diabetes and related cardiovascular disorders has led to the search for new pharmacological approaches in the treatment of these conditions. 1,2) In the early 1980s, the b3-adrenergic receptor (AR) was identified as a possible therapeutic target for the treatment of type II diabetes and obesity. 3,4) Early potent and selective b3-AR agonists, such as BRL-37344 5) and CL-316243, 6) were reported to be effective anti-obesity and anti-diabetic agents in rodents (Fig. 1). 7) Human clinical trials with these agents for the treatment of metabolic disorders, however, have been disappointing due to a lack of efficacy or an unfavorable sideeffect profile. 8,9) The clinical failure of such compounds has been attributed to a lack of sufficient b3-AR potency and selectivity relative to b1-and b2-ARs resulting from pharmacologic differences between rodent and human receptors, which was supported by the discovery, cloning, and characterization of the human, rat, and mouse b3-ARs. 10-12) Recent studies indicated that, in addition to adipocytes, the b3-AR is also distributed in human urinary bladder detrusor tissue and its relaxation occurs mainly via b3-AR. [13][14][15] The availability of appropriate human receptors has given rise to the design and synthesis of a new generation of b3-AR agonists with high potency. Subtype selectivity for b3-AR agonists must be kept specifically in mind, since activation of the b1-or b2-ARs would cause undesirable side effects such as increased heart rate or muscle tremors.We previously described efforts in this area, including the disclosure of acetanilide analogues exemplified by 2-pyridylacetanilide 1, which showed potent b3-AR agonistic activity with modest functional selectivity over b1-AR and oral hypoglycemic activity in diabetic kk mice (Fig. 2). 16) Compound 1 was found, however, to exhibit poor bioavailability in rats (Fϭ2%), probably due to the rapid metabolism of the 4-hydroxyphenoxy moiety on the left-hand side. Many kinds of phenylethanolamine-based b3-AR agonists have been reported (Fig. 3) 4,17) and we therefore decided to explore the alternative structures to the 4-hydroxyphenoxymethyl moiety. Subsequently, we attempted to modify the central part and the pyridyl moiety on the right-hand side (Fig. 2). In this paper, we describe the synthesis and structure-activity rela- Drug Discovery Research, Astellas Pharma Inc.; 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Received November 30, 2009; accepted January 26, 2010; published online January 27, 2010 In the search for potent and selective human b b3-adrenergic receptor (AR) agonists as potential pharmacotherapies for the treatment of obesity and non-insulin dependent (type II) diabetes, we prepared a novel series of phenylethanolamine derivatives containing acetanilides and evaluated their biological activities at the human b b3-, b b2-, and b b1-ARs. Among these compounds, the 6-amino-2-pyridylacetanilide (36b), 2-amino-5-methylthiazol-...

show abstract

“…Consequently, it is not possible to identify either of the synthetic products as the racemic form of a natural alkaloid. In order to avoid possible confusion in the future, and because of the obvious analogy with the dihydrocadambines (13,16,17), we shall refer to l b as decarbomethoxy-3a-nauclechine and to 19b as decarbomethoxy-3P-nauclechine, anticipating that both may eventually be isolated from natural sources.…”

Section: Decarbomethoxynauclechinementioning

confidence: 99%

The synthesis of Nauclea indole-pyridine alkaloids. 3,4-Disubstituted and 3,4,5-trisubstituted pyridines as synthetic intermediates; a total synthesis of (±)-decarbomethoxy-3α- and -3β-nauclechine

McLean¹

1983

Can. J. Chem.

Self Cite

View full text Add to dashboard Cite

Synthetic routes to a number of 3,4-disubstituted and 3,4,5-trisubstituted pyridines have been explored. These pyridines, designed to be used in the synthesis of Nauclea indole-pyridine alkaloids, are potentially useful intermediates in a number of syntheses. Particular attention has been paid to more highly substituted derivatives of 4-pyridineacetic acid, and the experimental limitations associated with their synthesis and use in subsequent reactions such as the Bischler–Napieralski cyclization have been described and explained. A synthesis of decarbomethoxynauclechine from 4-methylnicotinaldehyde avoiding these difficulties was then designed and executed. Both diastereoisomers, (±)-decarbomethoxy-3α-nauclechine and (±)-decarbomethoxy-3β-nauclechine, were obtained; the structure and stereochemistry of each was rigorously established, but it was not possible to demonstrate which corresponded to the natural alkaloid, decarbomethoxynauclechine, reported previously.

show abstract

Constituents of Naucleadiderrichii. Part VII. Synthesis of nauclederine, naucleonine, and naucleonidine; spectroscopic evidence for the structures of 3α-dihydrocadambine and two other constituents

Cited by 15 publications

References 3 publications

Neonaucline, a New Indole Alkaloid from the Leaves of Ochreinauclea maingayii (Hook. f.) Ridsd. (Rubiaceae)

Neonaucline, a New Indole Alkaloid from the Leaves of Ochreinauclea maingayii (Hook. f.) Ridsd. (Rubiaceae)

Synthesis and Evaluation of Novel Phenylethanolamine Derivatives containing Acetanilides as Potent and Selective .BETA.3-Adrenergic Receptor Agonists

The synthesis of Nauclea indole-pyridine alkaloids. 3,4-Disubstituted and 3,4,5-trisubstituted pyridines as synthetic intermediates; a total synthesis of (±)-decarbomethoxy-3α- and -3β-nauclechine

Contact Info

Product

Resources

About