A novel synthesis of (R)- and (S)-α-alkylated aspartic and glutamic acids: α-alkylated aspartic succinimides as new type of β-turn type II and II′ mimetics

Bicyclic peptides as type I/type II β‐turn scaffolds

“…A linear gradient from 20 to 80% of ( B ) over 40 rnin at flow rate of 114 mL/min was employed. The pooled fractions containing the desired product were lyophilized, affording 120 mg (0.138 mmol; yield was 28% based on the substitution level of the (6) 0.2219 (7) 0.2340 (6) 0.2057 (6) 0.1932 (7) 0.1699 (8) 0.0554 (7) 0.0308(8) 0.12 15 (7) 0.0865(9) 0.1520(9) 0.102( 1) 0.005( 1 ) 0.0592(9) 0.0208(6) 0.2899 (7) 0.2745(5) 0.3923(6) 0.4994 (7) 0.5589(9) 0.4937 (7) 0.443( 1) 0.376( 1) 0.360( 1) 0.414(1) 0.4740(9) 0.5760 (7) 0.6797(6) 0..5255 (7) 0.5916 (7) 0.6154 (7) 0.4941 (9) 0.5264(9) 0.4328(5) 0.5747 (7) 0.4983 (9) 0.760 (7) 0.9534 (6) 0.9156 (6) 1.0047 (7) 1.0943 (7) 1.1048 (7) 1.1548(4) 0.9803(6) 0.9045 (5) 1.0594 (6) 1.0465 (7) 1.1450 (7) 1.1656 (6) 1.1117 (7) 1.1572 (7) 1.2435 (8 (7) 1.0251 (7) 0.9682(5) 1.063 l(6) 1.0593 (7) 1.1504 (7) 1.1864(8) (7) 0.5388 (5) 0.9760 (5) 1.2597 (7) 1.2842 (9) 1.2300 (9) 1.1485 (9) 1.1300 (9) 1.0296 (7) 1.0683 (6) (2) Analytical RP-HPLC _ _ confirmed the purity of the product. FAB mass spectroscopy gave a molecular ion peak [M-HI' 868 amu as expected.…”

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

“…The reaction of benzaldehyde and ( S )-phenylglycinol in the presence of MgSO 4 (used as a dehydrating reagent) gave a chiral imine, and the subsequent Reformatsky reaction with bromide 7 afforded butyl acrylate 8 as a single diastereomer [11–12] (Scheme 2). Hydrolysis with CF 3 CO 2 H and converting the hydroxy group to the chloride yielded the corresponding lactam 9 [13]. The chiral auxiliary was removed by DBU-assisted elimination to the enamine and subsequent hydrolysis [14].…”

Synthesis, Conformational Properties, and Synthetic Applications of Novel Optically Pure α,α‐Disubstituted (R)‐ and (S)‐Glycines (‘α‐Chimeras’) Combining Side Chains of Asp, Glu, Leu, Phe, Ser, and Val

“…In addition of having the potential of altering the chemical properties by variation of the nature of the side chains R' and RZ (Fig. I), these amino acids can stabilize small peptides in rather well defined conformations by reducing the conformational flexibility of the backbone [6] [7]. .…”

“…While the conformational properties of cyclic and open-chain a,@-disubstituted (R)-and (S)-glycines bearing two non-functionalized side chains R' and R2 (Fig. 1 ) are quite well understood and range from stabilizing p-turn type-I [6] [8], type-I1 [7], and type-11' [7] [I 11, 3,"and a-helical [l l-151, and extended [16-201 conformations, the conformational properties of the parent disubstituted ( R ) -and (S)-glycines bearing functionalized and polar side chains have been much less investigated.…”

“…As part of a program of synthesizing and analyzing the conformational properties of disubstituted ( R )and (S)-glycines as conformationally restricted analogues of standard amino acids, we developed a general and high-yielding strategy towards the synthesis of a whole range of optically pure cyclic and open-chain a,a -disubstituted glycines [7-1 I]. This synthetic route provides a rapid and easy access to a-chimeras combining the side chains of functionalized amino acids like aspartic acid (Asp) [7], glutamic acid (Glu) [7], serine (Ser) [21], lysine (Lys) [15], and tyrosine (Tyr) [S]. Likewise, (R)and (S)-(amino-methy1)alanine (Ama) and ( R ) -and (S)-aminomethyl-leucine (Aml) [9] could be readily obtained.…”