Chemoenzymatic Synthesis and Synthetic Application of Enantiopure Aminocyclopentenols:  Total Synthesis of Carbocyclic (+)-Uracil Polyoxin C and Its α-Epimer

Abstract

Carbocyclic uracil polyoxin C (+)-2 and its alpha-epimer (-)-3 were synthesized in an efficient fashion from cis-4-(N-tert-butylcarbamoyl)cyclopent-2-en-1-ol (+/-)-7. The synthesis incorporates a concise, inexpensive chemoenzymatic synthesis of enantiopure aminocyclopentenols, a Pd(0)-catalyzed substitution reaction, and a mild reduction of an alpha-nitro ester by TiCl(3)/sodium borohydride. Significantly, this process demonstrates the synthetic utility of the versatile enantiopure aminocyclopentenol building block (-)-4.

Solid-Supported Nitroso Hetero Diels–Alder Reactions. 1. Acylnitroso Dienophiles: Scope and Limitations

“…Nitroso HDA reactions have become valuable and often key transformations in total syntheses of natural products such as the alkaloids narciclasin, 16 azimine, and carpaine, 17 as well as numerous biologically active compounds, 14,[18][19][20][21] including generation of novel N(4)-hydroxy-1,4-benzodiazepines. 22 There are numerous reports describing Diels-Alder reactions on solid-phase supports (reviewed, for example, in ref 23).…”

Hetero‐Diels‐Alder‐Reaktionen von Nitrosocarbonylverbindungen als nützliches Verfahren in der organischen Synthese

“…[66,[138][139][140][141][142][143] Das enantiomerenreine Acetat (À)-85, [105] das durch die in Abschnitt 6.2 beschriebene kinetische enzymatische Racematspaltung erhalten worden war, wurde zur Synthese des carbocyclischen Uracil Polyoxins C (129) und dessen Epimers über das Intermediat 128 verwendet (Schema 24). [140,144] Das Enantiomer des Acetats (À)-85 wurde für die Synthese des carbocyclischen Fragments des Nukleosids Q eingesetzt. [145] Cowart et al beschrieben außerdem eine Methode zur Synthese azacarbocyclischer Nukleosidanaloga, zum Beispiel 133 und 135, aus dem Cycloaddukt 83 (Schema 25).…”

Stereoselective Enzymatic Acylations (Transesterifications)

“…(38). This unnatural carbocyclic nucleoside is structurally related to natural antiviral and antitumor agents such as aristeromycin and neplanocin [107]. Brenna et al reported a lipase-mediated synthesis of (S)-and (R)-verapamil, a calcium channel blocker [108].…”