Synthesis of optically active homotryptophan and its oxygen and sulfur analogues

Synthesis of Optically Active Selenium‐Containing Isotryptophan, Homoiso­tryptophan, and Homotryptophan

“…Our retrosynthetic route is depicted in Scheme ; suitably substituted alkynyloxazolidines were used as building blocks for the introduction of a chiral center to the amino acids. We anticipated that selenoisotryptophan 5a and its higher homologue 5b could possibly be synthesized by iodocyclization3 of intermediate 4 , which could be obtained by Sonogashira coupling4 of iodophenyl methyl selenide ( 2 )3a,3b with alkynyloxazolidines 3a and 3b 5a–5d (retrosynthesis A, Scheme ). The synthesis of selenohomotryptophan 9 could be achieved from intermediate 8 , which in turn could be synthesized by Sonogashira coupling of 3‐iodobenzoselenophene ( 6 )3a and ethynyloxazolidine 7 6 (retrosynthesis B, Scheme ).…”

“…Moreover, the starting acetylene‐containing α‐amino acids were prepared by a chemoenzymatic method, as these compounds are very expensive commercially. Recently, we developed a strategy to prepare indole/benzofuran‐containing amino acids through the palladium‐catalyzed coupling of alkynyloxazolidines 5d,5e. At the onset of the synthesis, we prepared iodophenyl methyl selenide 2 3a,3b from commercially available 2‐iodoaniline.…”

“…Similarly, higher homologue 5b and iodo derivative 14b were prepared from butynyloxazolidine 3b and selenide 2 by following the reaction sequence shown in Scheme . Chiral acetylenes 3a and 3b were synthesized from naturally occurring L ‐aspartic acid and L ‐glutamic acid according to a literature procedure 5a–5d…”

Chiral Phosphoric Acid Catalyzed Enantioselective Friedel‐Crafts Reaction of N‐Protected 4‐Aminoindoles with β,γ‐Unsaturated α‐Ketimino Esters

“…For example, inhibition of indoleamine 2,3dioxygenase, [4] inhibition of adenosine deaminase, [5] inhibition of DNA methyltransferases, [6] and protein kinase C isozymes ( Figure 1). Representative examples of bioactive homotryptophan derivatives synthesis of homotryptophan derivatives often requires multi-step reactions using chiral pool approach, [6][7][8] or reductive amination of the corresponding chiral a-keto esters. Representative examples of bioactive homotryptophan derivatives synthesis of homotryptophan derivatives often requires multi-step reactions using chiral pool approach, [6][7][8] or reductive amination of the corresponding chiral a-keto esters.…”

“…We then chose the reaction of 1 a and 2 b as a model reaction, some other chiral phosphoric acids A2-A6 with different G groups have been screened (Table 1, entries [5][6][7][8][9], and A1 remains the best choice in term of stereoselectivity of the product 3 ab. A screening of the solvents revealed that the reaction worked well in aromatic solvents (toluene, o-xylene), but only trace amounts of product were detected when ethyl acetate was used most likely due to the hydrogen bonding of the solvent with the catalyst.…”