Amino acids bicyclic

From Ser via methyl 2-benzamido-3-chloropropionate, an azahexadiene was prepared which was photocyclized and hydrolyzed to the bicyclic amino acid 14 which is found in the Atelia Herbert Smithii plant (88JOC4793). 

Harwood and Lilley (87) reported the tandem generation and intramolecular trapping of a stabilized azomethine ylide, derived from the enantiopure template examined in detail in Section 3.2.3. Condensation of 5-hexenal with template 205 under standard conditions led to in situ ylide generation and subsequent cycloaddition of the tethered alkene to furnish 296 as a single enantiomer in 95% yield after purification and this despite the fact that the dipolarophile is unactivated. Hydro-genolytic destruction of the template revealed the bicyclic amino acid 297 in 75% yield (Scheme 3.97). 

Scheme 1.3.28 Asymmetric synthesis of bicyclic amino acids via Pauson-Khand cycloaddition of vinyl sulfoximines.

To conclude the asymmetric synthesis of the new bicyclic amino acids the protected amino acid 81 was treated with CF3SO3H in CH2CI2, affording the amino acid derivative 82 in high yield [51]. 

Palladium-mediated, Heck carbon-carbon bond formation has been used to introduce diversity via a scheme based on Pauson-Khand cyclizations, to generate fused bicyclic amino acid derivatives.47,48 The sequence of... 

Bolton, G. L. Hodges, J. C. Rubin, J. R. Solid Phase Synthesis of Fused Bicyclic Amino Acid Derivatives via Intramolecular Pausin-Khand Cyclisation Versatile Scaffolds for Combinatorial Chemistry, Tetrahedron 1997,53, 6611-6634. 

Title Aza-bridged Bicyclic Amino Acid Derivatives as a4 Integrin... 

In earlier investigations by the authors (2,3), benzylcyclobutyl-, (III), and bicyclic amino acid derivatives, (IV), respectively, were prepared, which were effective as high binding a28 subunit to a calcium channel, and used as anticonvulsants. 

Bicyclic amino acid derivatives, (III), prepared by Kozikowski (5) were effective as metabotropic glutamate receptor ligands and used in the treatment of neuronal cell damage associated with Parkinson s disease. 

In 1998, Kawahara and Nagumo reported the first total synthesis of a member of the TAN1251 series [63] and five years later both authors revisited the TAN1251A alkaloid by means of a new enantioselective synthesis (see Section 5.6). The retro synthetic analysis of TAN 1251A is outlined in Scheme 37. The target compound could be obtained by aldol reaction of tricyclic lactam 119, whose disconnection at the amide bond led to the bicyclic amino acid 120, which could be prepared from azaspirocyclic compound 121 by means of alkylation of the secondary amine and Mitsunobu-type chemistry. Azabicycle 121 may be prepared by an intramolecular alkylation of 122, which in turn could be available from allyl derivative 123. The latter can be prepared from carboxylic acid 124 by alkylation and subsequent Curtius rearrangement. 

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