2004
DOI: 10.1039/b401119h
|View full text |Cite
|
Sign up to set email alerts
|

Synthesis of tricyclic analogues of methyllycaconitine using ring closing metathesis to append a B ring to an AE azabicyclic fragment

Abstract: The synthesis of several ABE tricyclic analogues of the alkaloid methyllycaconitine 1 is reported. The analogues contain two key pharmacophores: a homocholine motif formed from a tertiary N-ethyl amine in a 3-azabicyclo[3.3.1]nonane ring system and a 2-(3-methyl-2,5-dioxopyrrolidin-1-ly)benzoate ester 4. The synthesis of the ABE tricyclic analogues of MLA 1 began with selective allylation at C-3 of 3 to produce allyl beta-keto ester 4. Double Mannich reaction of 4 with ethylamine and formaldehyde produced bicy… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
2

Citation Types

1
17
0

Year Published

2006
2006
2016
2016

Publication Types

Select...
4
2

Relationship

1
5

Authors

Journals

citations
Cited by 29 publications
(18 citation statements)
references
References 32 publications
1
17
0
Order By: Relevance
“…However, exceptions to these rules do exist as shown in Scheme 53, Scheme 54 and Scheme 55. [89][90][91][92][93] The basic amino groups of compounds 140a and 142a do not seem to be particularly hindered since the nitrogen atoms are attached to three adjacent secondary carbons. Surprisingly, these substrates underwent RCM in good to almost quantitative yields.…”
Section: Resultsmentioning
confidence: 98%
“…However, exceptions to these rules do exist as shown in Scheme 53, Scheme 54 and Scheme 55. [89][90][91][92][93] The basic amino groups of compounds 140a and 142a do not seem to be particularly hindered since the nitrogen atoms are attached to three adjacent secondary carbons. Surprisingly, these substrates underwent RCM in good to almost quantitative yields.…”
Section: Resultsmentioning
confidence: 98%
“…The synthesis started from allylated β-keto ester 6 [14] that underwent facile double Mannich reaction with bis(aminol) ether 7 [19] using methyltrichlorosilane as the activator in acetonitrile at ambient temperature providing an efficient method for construction of the N-(3-phenylpropyl)-substituted azabicyclo[3.3.1]-nonane 8. [19] Sodium borohydride reduction of the ketone 8 then afforded the secondary alcohol 9 in 46 % yield together with the alcohol 10 in 33 % yield, which were readily separated by flash chromatography.…”
Section: Resultsmentioning
confidence: 99%
“…[10] All four diastereomers showed the same potency at both the α3 and α7 nicotinic acetylcholine receptors as the racemic compound. We have previously reported [14] the synthesis of several tricyclic analogues of 1 containing the key 2-(3-methyl-2,5-dioxopyrrolin-1-yl)benzoate ester in which an additional seven-membered ring (a B ring) was appended to a 3-azabicyclo[3.3.1]nonane framework (the AE rings) envisaging that incorporation of the N-substituted anthranilate ester into a conformationally restricted framework might enhance the biostability, selectivity and potency of previously prepared simpler bicyclic AE analogues. We have also recently reported that bis-aminoalkylation of cyclic β-keto esters using bis(aminol) ethers provides an efficient entry to azabicyclo[3.3.1]nonanes.…”
Section: Introductionmentioning
confidence: 98%
See 2 more Smart Citations