Junhua Tao

A simple, stereoselective synthesis of ketomethylene dipeptide isosteres

Abstract An exceedingly simple, general, and stereoselective method for the preparation of ketomethylene dipeptide isosteres (5-(carbobenzyloxyamino)-2-alkyl-γ-ketoesters) from Cbz-protected amino acids and scalemic 2-triflyloxy esters has been developed. The method is short (three steps), efficient, and highly diastereoselective and enantioselective.

A Stereocontrolled Synthesis of Monofluoro Ketomethylene Dipeptide Isosteres.

A simple, stereocontrolled synthesis of monofluoro ketomethylene dipeptide isosteres has been developed. N-Tritylated ketomethylene dipeptide isosteres, prepared from N-tritylated amino acids, are converted to their Z-TMS enol ethers and fluorinated with Selectfluor. There is cooperative stereocontrol between the N-tritylamine group and the alkyl group at C-2. The method is short (six steps), diastereoselective (85 --> 95%), and enantioselective (>95%).

A short, enantiospecific synthesis of a protected seco acid precursor to (R,R)-(−)-pyrenophorin

Abstract Described herein is a four-step enantiospecific synthesis of a protected seco acid precursor of (R,R)-(−)-pyrenophorin in 23% yield from a chiral β-ketoester 3 , which can be prepared in one step from ethyl acetoacetate by a standard procedure.

A stereocontrolled synthesis of monofluoro ketomethylene dipeptide isosteres

Abstract A simple, stereocontrolled synthesis of monofluoro ketomethylene dipeptide isosteres has been developed. The method is short (6 steps) and diastereoselective (85–95% de) and enantioselective (>95% ee).

Synthesis of D-erythro-sphingosine and D-erythro-sphinganine via 3-ketosphinganine

D-erythro-sphingosine and D-erythro-sphinganine can be produced in protected form from serine by a synthetic approach in which the normal biological intermediate 3-ketosphinganine in protectyed form, is a key synthetic intermediate. The sequence is short and convergent, proceeds in good overall yields (≈30% for 6 steps) and with excellent stereocontrol (>91% de, >95% ee).

Synthesis of Cbz-Protected Ketomethylene Dipeptide Isosteres

Ketomethylene peptide isosteres have been the focus of a variety of synthetic studies because of their potential as therapeutic agents in the treatment of medical conditions mediated by proteases (1-3). The dipeptide core units 1 are chemically characterized by a 1,4-disposition of the carbonyl groups (ketone and carboxylate) and have an alkyl group at C-2 that is a chiral center. Protecting groups at amino nitrogen (typically carbamate such as Cbz or Boc) and the carboxyl group (typically ester) are usually present to make processing easier but must be readily and independently removable to permit extension in either the N-terminal or C-terminal directions (Fig. 1). Figure 1.