Enantiospecific and diastereoselective synthesis of 4,4-disubstituted-3-amino-2-azetidinones, starting from D-serine

Ageno, G.; Banfi, Luca; Guanti, Giuseppe; Manghisi, E.; Riva, Renata; Rocca, Valeria

doi:10.1016/0040-4020(95)00427-a

Cited by 49 publications

(38 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This alcohol was synthesized from D-serine in five steps according to a literature procedure. 45 Treatment of D-serine with di-tert-butyl dicarbonate and NaHCO 3 protected the amino group as its Boc carbamate, and the carboxylic acid was then coupled with N,Odimethylhydroxylamine to afford Weinreb amide 17 using 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI·HCl) as the coupling reagent. The amino and hydroxyl groups of 17 were protected as the N-tert-butoxycarbonyl-N,O-isopropylidene derivative.…”

Section: The Challengesmentioning

confidence: 99%

Evolution of the Total Syntheses of Ustiloxin Natural Products and Their Analogues

Evans

et al. 2008

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Ustiloxins A-F are antimitotic heterodetic cyclopeptides containing a 13-membered cyclic core structure with a synthetically challenging chiral tertiary alkyl-aryl ether linkage. The first total synthesis of ustiloxin D was achieved in 31 linear steps using an S N Ar reaction. An nOe study of this synthetic product showed that ustiloxin D existed as a single atropisomer. Subsequently, highly concise and convergent syntheses of ustiloxins D and F were developed by utilizing a newly discovered ethynyl aziridine ring-opening reaction in a longest linear sequence of 15 steps. The approach was further optimized to achieve a better macrolactamization strategy. Ustiloxins D, F and eight analogues (14-MeO-ustiloxin D, four analogues with different amino acid residues at the C-6 position, and three (9R, 10S)-epi-ustiloxin analogues) were prepared via the second generation route. Evaluation of these compounds as inhibitors of tubulin polymerization demonstrated that variation at the C-6 position is tolerated to a certain extent. In contrast, the S configuration of the C-9 methylamino group and a free phenolic hydroxyl group are essential for inhibition of tubulin polymerization. Antimitotic agentsAntimitotic agents have long been of interest to scientists and physicians, even before their precise mechanism of action could be articulated. Most of these compounds interfere with microtubule assembly and functions thus resulting in mitotic arrest of eukaryotic cells. There are a number of natural and synthetic compounds that interfere with tubulin function to inhibit the formation of microtubules. 1 Such antimitotic agents exhibit a broad range of biological activities and can be used for medicinal and agrochemical purposes, acting as anticancer, antifungal, or anthelmintic agents. Moreover, tubulin binding compounds are valuable for understanding basic mechanisms involved in the dynamics of the microtubule network. 2 Mitotic arrest is of importance in cancer chemotherapy, since tubulin is an established chemotherapeutic target. In addition to the widely used vinca alkaloids and taxoids, many other antimitotic agents are currently in clinical or preclinical development. 3 Newer potential targets NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript that may cause mitotic arrest are in development as well. Although cancer chemotherapy is a very important goal being extensively investigated, the mechanism of action of the naturally occurring peptides that inhibit tubulin polymerization remains a challenging problem. Attempts to establish a relationship among the tubulin binding peptides have only had limited success. [4][5][6][7][8] As a result, the mechanism of action of peptidic antimitotic agents is not completely elucidated and deserves further investigation. UstiloxinsThe first peptide shown to interact with tubulin was phomopsin A (Error! Reference source not found.). [9][10][11][12][13] Since then, a number of peptides and depsipeptides were found to disrupt cellular microtubules. These compo...

show abstract

Section: The Challengesmentioning

confidence: 99%

Evolution of the Total Syntheses of Ustiloxin Natural Products and Their Analogues

Evans

et al. 2008

J. Am. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…Compound 5 has been prepared before by an independent method. [20] An X-ray structure of the racemic compound is available. [21] Alkynylation of 5 afforded key intermediate 6 in 50% yield.…”

Section: Resultsmentioning

confidence: 99%

“…The diastereomeric ratio of 2:1 is in agreement with the assumption of nonchelating reaction conditions and with published data on related reactions. [20] The alternative order of alkylation/alkynylation reactions turned out to be less suitable in terms of overall yield: Alkynylation of Garner's aldehyde with an alkynyllithium compound to 7, [22Ϫ24] and the subsequent Swern oxidation to amino ketone 8 proceeded in satisfactory yield. However, the Grignard reaction leading to 6 was only achieved in low yields.…”

Section: Resultsmentioning

confidence: 99%

“…The diastereoselectivity of the reaction as determined by NMR spectroscopy favors the anti-Felkin product in a 2.5:1 ratio and can be explained by the assumption of chelate control of the reaction. [20] The subsequent synthetic steps utilize 6, which has been prepared via the intermediates 4 and 5. For the synthesis of the target compounds 2a and 2b in -erythro and -threo configurations, respectively, alkyne 6 was deprotected to 9 with HCl in THF [20] in 86% yield (Scheme 3).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Syntheses of 3‐C‐Methylceramides

Sawatzki

Kolter

2004

Eur J Org Chem

View full text Add to dashboard Cite

show abstract

“…Longer reaction times did not improve the conversion and when the reaction was carried out at higher temperatures the yield dropped considerably. It is worth mentioning that Guanti and co-workers reported that compound 4 showed a poor reactivity upon the addition of several organometallic reagents such as ethyl-and vinyllithium [12].…”

mentioning

confidence: 99%

Nucleophilic Additions of 2-Furyllithium to Carbonyl Derivatives of L-Serine. Formal Synthesis of (2R,3R)-β-Hydroxy Aspartic Acid

et al. 1998

View full text Add to dashboard Cite

show abstract

Enantiospecific and diastereoselective synthesis of 4,4-disubstituted-3-amino-2-azetidinones, starting from D-serine

Cited by 49 publications

References 53 publications

Evolution of the Total Syntheses of Ustiloxin Natural Products and Their Analogues

Evolution of the Total Syntheses of Ustiloxin Natural Products and Their Analogues

Syntheses of 3‐C‐Methylceramides

Nucleophilic Additions of 2-Furyllithium to Carbonyl Derivatives of L-Serine. Formal Synthesis of (2R,3R)-β-Hydroxy Aspartic Acid

Contact Info

Product

Resources

About