Asymmetric synthesis of 1,3-thiazolidine-derived spiro-β-lactams via a Staudinger reaction between chiral ketenes and imines

Cremonesi, Giuseppe; Croce, Piero Dalla; Fontana, Francesco; Forni, Alessandra; Rosa, Concetta La

doi:10.1016/j.tetasy.2005.08.054

Cited by 32 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it was concluded that the formation of a mixed acid anhydride and the epimerization at C4 are avoided under these conditions using an inorganic base as in the case of the 4-methyl ester derivative reported by Cremonesi et al, 24) and that N-acetylation proceeded with retention of the C4 configuration. Similarly, another set of stereoisomers of CP2Et (2c, d)…”

Section: Cis-(2r4r)-accp2et (4a) and Trans-(2s4r)-accp2et (4b)mentioning

confidence: 87%

“…21) Conversely, Cremonesi et al reported that the acetylation of (2S,4R)-1,3-thiazolidine-2,4-dicarboxylic acid 4-methyl ester with acetyl chloride in the presence of trimethylamine (Et 3 N) in dichloromethane afforded (2S,4R)-3-acetyl-1,3-thiazolidine-2,4-dicarboxylic acid 4-methyl ester with retention of configuration at C4 because their substrate could not generate an acid anhydride intermediate involving the 4-carboxyl group. 24) Conversely, little information is available about the stereoselectivity of CP derivatives in N-acetylation, i.e., 2,2-disubstituted thiazolidine-4-carboxylic acid. The CP derivative also comprises four stereoisomers.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Synthesis, Characterization, and Evaluation of Thiazolidine Derivatives of Cysteine for Suppressing Eumelanin Production

Amino

Takino

Kaneko

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

In the pathway of melanin biosynthesis, cysteine (Cys) is utilized for the synthesis of pheomelanin. Accordingly, Cys is considered to suppress the formation of brown-black eumelanin. Although attempts have been made to utilize Cys and its derivatives as skin-whitening agents, their instability and odor hinders their application as a cosmetic agent. Herein, N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid ethyl ester (AcCP2Et) was proposed as a candidate for a stable and prolonged-release derivative of Cys to inhibit dopachrome formation after its degradation in melanocytes. It was synthesized by acetylation of 2-methylthiazolidine-2,4-dicarboxylic acid 2-ethyl ester (CP2Et), the condensation derivative of Cys and ethyl pyruvate. AcCP2Et suppressed melanogenesis in melanocytes in vitro, was stable in phosphate buffer at 70°C for five days, and exhibited far less odor than CP2Et. Therefore, AcCP2Et was validated to be a useful deriative of Cys for application as a skin-whitening agent. AcCP2Et comprises four stereoisomers; thus characterization of each stereoisomer was required. The stereochemistry of AcCP2Et was confirmed via a single-crystal X-ray structure analysis of N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid (AcCP) derived from AcCP2Et. In the synthesis of AcCP2Et, the acetylation of CP2Et proceeded with epimerization at C4 to give trans-isomers when excess acetyl chloride and an organic amine was used, whereas it proceeded while retaining the original (R) configuration at C4 to give the cis-and trans-isomer when an equivalent of acetyl chloride with an inorganic base was used. These results indicate that the formation of an intermolecular mixed acid anhydride is responsible for the isomerization at the C4 asymmetric center.Key words thiazolidine derivative; cysteine; suppressing eumelanin production; acetylation; stereoisomer Melanin plays an important role in determining hair, eye, and skin color. It also protects the skin from UV radiation and inhibits photocarcinogenesis. 1) However, hyperpigmentation, which is caused by melanin overproduction and accumulation, causes freckles, age spots, melisma, and melanoma. 2)Medical cosmetics that contain skin-whitening components are used for treating hyperpigmentation. The inhibitory effect of conventional pharmaceutical skin-whitening agents such as hydroquinone, arbutin, 3) and kojic acid 4) on melanogenesis is attributed to the inhibition of tyrosinase. Therefore, skin-whitening agents that have a mechanism distinct from tyrosinase inhibition should be useful.Melanin is produced in human pigment cells (melanocytes) in the skinutilizing L-tyrosine (Tyr) and L-cysteine (Cys). The melanin biosynthesis pathway comprises two main parts: the production of eumelanin and the production of pheomelanin. During eumelanogenesis, Tyr is converted to 3,4-dihydroxyphenylalanine (DOPA) by tyrosinase, which then further catalyzes the conversion of DOPA to dopaquinone. Dopaquinone is converted to 5,6-dihydroxyindole-2-carboxylic acid and 5,6-dihydroxyindole intermedi...

show abstract

Section: Cis-(2r4r)-accp2et (4a) and Trans-(2s4r)-accp2et (4b)mentioning

confidence: 87%

mentioning

confidence: 99%

Synthesis, Characterization, and Evaluation of Thiazolidine Derivatives of Cysteine for Suppressing Eumelanin Production

Amino

Takino

Kaneko

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…As depicted in Figure , the complete regio- and stereoselectivity observed was explained by the endo approach of the E -nitrone to the double bond from the less hindered side of the pyrroline ring. The β-lactam ring is perpendicular to the pyrroline ring as highlighted by X-ray analysis of very similar compounds . Its presence, and in particular the steric hindrance of the C-phenyl group, could direct the nitrone attack from the less hindered side that is opposite to the C-phenyl group.…”

Section: Resultsmentioning

confidence: 99%

“…In particular, we were interested in producing various substituted 4-spiro-β-lactams by means of a Staudinger reaction between imines and nonsymmetrical cyclic ketenes generated from cyclic N -acyl α-amino acids. At the same time, we also realized the stereoselective synthesis of 4-spiro-β-lactams using ketenes obtained from chiral, enantiomerically pure N -acyl α-amino acids. , …”

Section: Introductionmentioning

confidence: 99%

Enantiomerically Pure Polyheterocyclic Spiro-β-lactams from trans-4-Hydroxy-l-proline

Cremonesi¹,

Croce

Fontana

et al. 2010

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

The "Staudinger ketene-imine reaction" between ketenes generated from natural O,N-protected trans-4-hydroxy-l-prolines and the N-benzyl-N-benzylideneamine led to mixtures of diastereoisomeric, enantiomerically pure pyrrolidine-derived spiro-beta-lactams with a relative cis configuration. These were transformed into the corresponding pyrroline-spiro-beta-lactams by means of treatment with a base and the new C=C double bond was submitted to a number of different reactions in order to evaluate its reactivity and obtain new polyheterocyclic enantiomerically pure spiro-beta-lactams.

show abstract

“…89 There are many methods for the construction of the azetidinone ring; for example, rhodium-catalyzed carbonylation of an aziridine, 90 rhodiumcatalyzed intramolecular insertion of an α-diazo amide into a C− H bond, 91 copper-catalyzed coupling of an alkyne with nitrone, 92 amino-ether-catalyzed reaction of ester enolates with imines, 93 and ketene−imine cycloaddition. 94 Among these, the anellation of acetyl chlorides with imines has proven to be a versatile and convenient procedure. Chen et al 95 prepared β-lactams 179 from two steps: (a) generation of ketenes in situ, by dehydrohalogenation of acethyl chlorides 177 in the presence of ionic liquid (IL) and Yb(OTf) 3 ; and (b) [2 + 2] cyclocondensation of imines 178 with ketenes (Scheme 1).…”

Section: Cyclocondensation Reactionsmentioning

confidence: 99%

Update 1 of: Ionic Liquids in Heterocyclic Synthesis

et al. 2014

View full text Add to dashboard Cite

Asymmetric synthesis of 1,3-thiazolidine-derived spiro-β-lactams via a Staudinger reaction between chiral ketenes and imines

Cited by 32 publications

References 36 publications

Synthesis, Characterization, and Evaluation of Thiazolidine Derivatives of Cysteine for Suppressing Eumelanin Production

Synthesis, Characterization, and Evaluation of Thiazolidine Derivatives of Cysteine for Suppressing Eumelanin Production

Enantiomerically Pure Polyheterocyclic Spiro-β-lactams from trans-4-Hydroxy-l-proline

Update 1 of: Ionic Liquids in Heterocyclic Synthesis

Contact Info

Product

Resources

About