Efficient preparation of 2,4-methanoproline

Recent Advances in the Synthesis of Cyclobutanes by Olefin [2 + 2] Photocycloaddition Reactions

“…In this context, several studies were concerned with an improved photochemical access 682 to 2,4-methanoproline and its derivatives. 683 − 685 Mykhailiuk et al employed an intramolecular [2 + 2] photocycloaddition reaction to the synthesis of 4-fluoro-2,4-methanoproline ( rac - 380 ). 686 Sensitized irradiation of acrylate 378 led to the ester of the N -protected product rac - 379 , which was hydrolyzed to the target compound rac - 380 ( Scheme 123 ).…”

4‐(Di‐/Trifluoromethyl)‐2‐heterabicyclo[2.1.1]hexanes: Advanced Fluorinated Phenyl Isosteres and Proline analogues

“…acids 17 a and 17 b are by ca. 1.3 pK a units more acidic as compared to benzoic acid (26); expectedly, they are also by ca. 0.7 pK a units more acidic than their non-fluorinated counterpart 17 c. In addition to that, anilides 27 a-c and 28 were also synthesized, and their aqueous solubility (S w ) and octanolwater partitioning coefficient logarithm (LogP) values were established using the shake-flask method (Scheme 7).…”

“…In particular, this framework is a part of a naturally occurring non-proteinogenic amino acid -2,4-methanoproline, a target for numerous synthetic studies. [17][18][19][20][21][22][23][24][25][26] Relevance of the 2,4-methanopyrrolidine scaffold to medicinal chemistry was also outlined. [20,[27][28][29] It is widely recognized that introducing fluorinated substituents into potential biologically active compounds can finetune their physico-chemical parameters, improve metabolic stability, and provide additional opportunities for interactions with a biological target.…”

Escaping from Flatland: Substituted Bridged Pyrrolidine Fragments with Inherent Three-Dimensional Character

“…We have, like other workers, focused some of our efforts on analogues of 2,4-methanoproline 1 . 2,4-Methanoproline 1 was first isolated from the seeds of Ateleia herbert smithii Pittier, a tree found in Costa Rica, and is prepared in a simple sequence of reactions from ethyl pyruvate 2 or serine 3 (Scheme ) via intramolecular [2 + 2] olefin photocycloaddition reactions. , The utility and conformational properties of 2,4-methanoproline 1 as a replacement for d - or l -proline have been studied; its N -acetyl, methyl ester was found to show a large prevalence for a trans -amide conformation more akin to primary amino acids than to d - or l -proline . This makes it a potentially interesting amino acid for inclusion in therapeutic peptides and the basis for the design of fragment libraries.…”