Acyclic amino acids synthesis

A formal total synthesis of the early carbapenem antibiotics thienamycin 217 and PS-5 218 from an acyclic amino acid derivative has been reported <1996JOC2413>. For a cycloaddition process from acyclic compounds, see Section... 

The aldol reaction in the presence of an acyclic amino acid has been harnessed in total synthesis. Takabe reported the organocatalytic ot-hydro)ymethylation of a cyclic ketone in aqueous formaldehyde with L-threonine, as the key step for the formal synthesis of chiral jasmine lactone. In a similar way, the team of Chen and Chai prepared several cyclohexanone derivatives. Much more recently, a synthesis of phaitanthrin A by aldol reaction of tryptanthrin with acetone in the presence of the potassium salt of L-phenylalanine has been performed in gram-scale quantities. Numerous derivatives have been obtained with yields of up to 98% and ee of up to 99%. 

Recently, Charette et al. have also demonstrated this behavior in the stereoselective cyciopropanations of a number of enantiopure acyclic allylic ethers [47]. The high degree of acyclic stereocontrol in the Simmons-Smith cyclopropanation has been extended to synthesis several times, most notably in the synthesis of small biomolecules. Schollkopf et al. utilized this method in their syntheses of cyclopropane-containing amino acids [48 a, b]. The synthesis of a cyclopropane-containing nucleoside was also preformed using acyclic stereocontrol [48c]. 

Brzezinska KR, Deming TJ (2001) Synthesis of ABA triblock copolymers via acyclic diene metathesis polymerization and living polymerization of alpha-amino acid-N-carboxyanhy-drides. Macromolecules 34 4348 354... 

Evidently, an increase in steric hindrance around the reduced fragment requires the presence of ammonium fluoride in the reaction mixture. It should be noted that potassium fluoride has no effect. It is highly probable that ammonium fluoride is required for slow elimination of HF, which gradually desilylates the nitroso acetal fragment thus facilitating its reduction. As can be seen from Scheme 3.284, many reduction products are derivatives of unnatural amino acids. Since the initial nitroso acetals can be prepared by silylation of simple acyclic AN, possibilities have been opened for the synthesis of unnatural amino acids from available AN. 

Diastereoselective 1,4- and 1,6-addition reactions of lithium amides to chiral naph-thyloxazolines were used by Shimano and Meyers108-110 for the synthesis of novel amino acids. For example, treatment of (S )-2-(l-naphthyl)-4-t-butyloxazoline with lithi-ated l,4-dioxa-8-azaspiro[4.5]decane and iodomethane provided the diastereomerically pure 1,4-addition product with excellent yield cleavage of the heterocyclic rings then gave the desired /3-amino acid (>99% ee/ds equation 32)108,109. In contrast to this, most acyclic lithium amides reacted with these oxazolines under 1,6-addition the products were transformed smoothly to 5-amino acid derivatives (equation 33)110. 

Recently, Scialdone and colleagues have employed phosgenated />-nitrophenyl(poly-styrene) ketoxime (Phoxime, 76) resin in the synthesis (via 77 and 78) of acyclic and heterocyclic amino-acid-derived ureas 79 too (Scheme 42). Resin 75 was first reacted with an amino acid and TMSCl in pyridine, and the resulting carbamate acid resin 77 was then coupled with an amine under standard carbodiimide protocol (HOBt/DIC in DMF) to obtain the carbamate amide resin 79. 

Inhibition of Chorismate Synthase Shikimic and quinic acids are used by microorganisms, fungi, and superior plants for the synthesis of essential aromatic amino acids from acyclic sugars. Fluorinated analogues of substrates and reaction intermediates have been synthesized in order to inhibit enzymes involved in... 

Cycloaddition to endocyclic unsaturation has been used by many researchers for the preparation of isoxazoUdinyl adducts with y-lactams derived from pyrogluta-minol and is discussed later in this chapter as a synthesis of unusual amino acids (Scheme 1.20, Section 1.6) (79,80). A related a,p-unsaturated lactam has been prepared by a nitrone cycloaddition route in the total synthesis of the fungal metabolite leptosphaerin (81). A report of lactam synthesis from acyclic starting materials is given in the work of Chiacchio et al. (82) who prepared isoxazolidine (47) via an intramolecular nitrone cycloaddition reaction (Scheme 1.11). 

The acyclic sulfonimidoyl-substituted amino acids 24 were selected as starting material for the synthesis of the unsaturated prolines of type 63. Because of the facile synthesis of the unsaturated bicyclic tetrahydrofurans 53 from the vinyl aminosulfoxonium salts 46 (cf. Scheme 1.3.20), it was speculated that upon treatment with a base the vinyl aminosulfoxonium salts 67 would experience a similar isomerization with formation of the allyl aminosulfoxonium salts 69, which in turn could suffer an intramolecular substitution of the allylic aminosulfoxonium group (Scheme 1.3.24). The methylation of sulfoximines 24 with Me30Bp4 gave... 

Therefore we were interested in the development of a method for the asymmetric synthesis of cyclic and acyclic 5-hydroxy-P-amino acids 83-85 (Fig. 1.3.8). 

Scheme 1.3.29 Asymmetric synthesis of protected acyclic 5-hydroxy-P-amino acids...

Cativiella, C. Diaz-De-Villegas, M. D. Stereoselective Synthesis of Quaternary a-Amino Acids. Part 1. Acyclic Compounds, Tetrahedron Asymmetry 1998, 9, 3517-3599. 

The addition of HCN to aldehydes has been a well-known reaction since the 19th century, especially in the context of the Kiliani-Fischer synthesis of sugars. Even older is the Strecker synthesis of amino acids by simultaneous reaction of aldehydes with ammonia and HCN followed by hydrolysis. The challenge in recent years has been to achieve face-selectivity in the addition to chiral aldehydes. These face-selective additions, known as nonchelation-controlled processes, refer to the original formulation of Cram s for the reaction of nucleophiles with acyclic chi carbonyl compounds. The chelation-controlled reactions refer also to a formulaticxi of Cram s, but whose stereochemical consequences sometimes differ. 2... 

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