Total Synthesis of (±) Carbocyclic Polyoxin C and Its α-Epimer

Abstract

Carbocyclic polyoxin C (2) and its alpha-epimer 3 were synthesized in racemic form in an efficient and diastereodivergent fashion from cis-4-(N-tert-butylcarbamoyl)cyclopent-2-en-1-ol (5a). This synthesis features a Pd(0)-catalyzed substitution reaction, a novel, mild reduction of an alpha-nitro ester to an amino acid ester, and an improved procedure for uracil ring formation.

Stereoselective Synthesis of Enantiopure Cycloalkylglycines by 1,3‐Dipolar Cycloaddition of a Chiral Nitrone to Cycloalkenes

“…Upon heating under microwave activation (160°C) for 2 h, cycloadduct 3c disappeared (TLC) to afford a more-polar product. The solution was concentrated, and the residue was purified by C 18…”

“…[5] More recently, we have reported a new route toward unprecedented 3-substituted 4-hydroxyproline derivatives and (αS,3R,4S)-4-hydroxy-3-glycinylpyrrolidine. [12] A survey of the chemical literature concerning cyclic αamino acids reveals a variety of synthetic methods [18][19][20][21][22][23] that are different from the synthetic strategy reported herein. Many of these cycloalkylglycines have important biological roles, such as the prevention and treatment of disorders of fat metabolism and obesity, [24] the treatment of neuropathic pain, [25] and the treatment of carbohydrate or lipid metabolism disorders, including diabetes.…”

Catalytic Asymmetric Hetero Diels–Alder Reactions of N‐Sulfinyl Dienophiles with Chiral Bis(oxazoline)copper(II) and ‐zinc(II) Triflates

“…A distinct drop in de and ee was observed in reactions with 10 mol-% loading of ent-4a-Cu(OTf) 2 (ent = enantiomer), as shown in Table 1, Entries 1 and 2 for Nsulfinyl 1a and 1b, respectively. Better results were obtained with ent-4a-Zn(OTf) 2 ( [11] A stereochemical model involving a bidentate coordination of N-sulfinyl dienophile 1a or 1b to the chiral Lewis acid with the sulfinyl oxygen and the carbonyl oxygen or one of the sulfonyl oxygens, respectively, might explain the excellent stereochemical outcome in the stoichiometric catalyst reactions. [7a] Similarly, a strong (O,O) chelate for the HDA adducts 3a or 3b and the chiral Lewis acid will also explain an inhibited catalyst turnover in the catalytic reactions.…”

Enantioselective synthesis of (1 S ,4 R )- N -(benzylcarbamoyl)-4-aminocyclopent-2-en-1-ol by Candida antarctica lipase B

“…Although the biological synthesis of typical 5 0 -(hydroxymethyl) cyclopentane derivatives [10,11] and 2-cyclopentene-1,4-diol derivatives [12][13][14] have been explored and discussed in many published reports, insufficient research has been targeted at 4-aminocyclopent-2-en-1-ol. Limited biological methods are available to give access to structurally diverse carbocyclic nucleosides, such as polyoxins and nikkomycins [15]. Therefore, it is necessary to devise efficient and inexpensive biocatalytic processes for 4-aminocyclopent-2-en-1-ol precursors.…”