Stereoselective total synthesis of (+)-lactacystin from d-glucose

Enantio‐ and Diastereoselective Construction of α,α‐Disubstituted α‐Amino Acids for the Synthesis of Biologically Active Compounds

“…Ozone was found to be a much superior oxidant than [56] The resulting amino acid 40 was then converted into Corey's intermediate 41 (Scheme 8). [32] To date, the total synthesis of lactacystin has been accomplished by Omura, Smith III, and Sunazuka et al, [42] Baldwin et al, [43] Chida et al, [51] and Kang et al [47] Since two reviews on their synthesis, excluding Kang's work, have been reported, [70] this review deals with methods to construct the key quaternary stereogenic center at C5, as shown in Scheme 9. Omura's group [42] has employed the aldol condensation of an ester enolate derived from trans-oxazoline 42 with formaldehyde.…”

“…A different mode for the construction of the C5 stereogenic center was employed by Chida and coworkers. [51] Upon heating of trichloroacetimidate 48 derived from -glucose, the reaction underwent an Overman rearrangement [50] to give allylamine 49 as a 4:1 mixture of diastereomers. Kang's group [47] has employed the trichloroacetimidate 51 for a mercuriocyclization reaction to construct the key C5 stereogenic center of lactacystin.…”

“…The intriguing methods applied to the construction of a quaternary carbon center with an amino group in the target molecule ( Figure 1) include a nucleophilic addition of cyanide to the ketimine intermediate using an asymmetric Strecker synthesis for various α-substituted serine analogs (1), [29][30][31] (+)-LY-354740 (2), [12] Leu-Enk analogs (3), [13] lactacystin (4) (Corey's intermediate), [32] manzacidins (5), [33] kaitocephalin (6), [34] and altemicidin (7) intermediate, [35] a sulfonamide-derived nitrene insertion into the C-H bond for manzacidins (5), [36] a Diels-Alder cycloaddition to an α,β-unsaturated amino ester for altemicidin (7), [37] a Lewis acid-induced Hatakeyama epoxide opening [38] for lactacystin (4) [39] and sphingofungins (9), [40] an aldol condensation of an enolate derived from an α-amino ester with an aldehyde for lactacystin (4), [41][42][43][44] kaitocephalin (6), [45] and neooxazolomycin (10), [46] a mercuriocyclization of an allylic trichloroacetimidate for lactacystin (4), [47] an aldol condensation of bislactim [48] and a Pd-catalyzed alkylation of oxazoline ester [49] for sphingofungin F (9b), an Overman rearrangement [50] for lactacystin (4) [51] and sphingofungin E (9a), [52] and other methods, as shown in Figure 2. The discussion below is limited mainly to key methods for the construction of a quaternary carbon center attached to an amino group, as employed for the synthesis of the target molecules in Figure 1 based on our work and that of others.…”

Peptide and Peptide-Like Modulators of 20S Proteasome Enzymatic Activity in Cancer Cells

“…A substantial effort was devoted to the total synthesis of lactacystin, and the successful identification of different synthetic routes (Corey and Reichard, 1992 ; Corey et al., 1993 ; Sunazuka et al., 1993 ; Uno et al., 1994 ; Chida et al., 1995 ; Nagamitsu et al., 1996 ; Chida et al., 1997 ; Corey et al., 1998 ;) allowed the preparation of lactacystin analogs (e.g., compound 28 , Figure 7 ) (Soucy et al., 1999 ) and initial studies on the molecular basis of its selectivity and potency (Corey et al., 1999 ). The initial SAR data revealed that the original groups at C5 and C9 seem to be optimal for proteasome inhibition and only the replacement of the 7-methyl substituent by ethyl, n -butyl or isopropyl improved 2- to 2.8-fold the chymotrypsin-like peptidase inhibitory activity of the parent compound.…”

Synthesis and Neurotrophic Activities of N‐p‐Tolyl/phenylsulfonyl L‐Amino Acid Thiolester Derivatives

“…OM-6519 in 1991 [8][9][10] and elucidated as the novel γ-lactam thiolester structure through spectral data and X-ray analysis. [11][12][13][14][15] Lactacystin was thought to be a small molecular mimic of nerve growth factor. [16][17][18][19] Several research groups undertook the total syntheses of lactacystin.…”