534584-71-9Relevant academic research and scientific papers
Cyclopropyl and cyclobutyl epothilone analogs
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Page/Page column 5-6; 10; 3/16, (2008/06/13)
The invention relates to cis- and trans-12, 13-cyclopropyl and 12,13-cyclobutyl epothilones of formula I to IV wherein Ar is a radical represented by the following structure: and the other radicals and symbols have the meanings as defined herein; to their
A systematic study of the hydride reduction of cyclopropyl ketones with structurally simplified substrates. Highly stereoselective reductions of trans-substituted cyclopropyl ketones via the bisected s-cis conformation
Kazuta, Yuji,Abe, Hiroshi,Yamamoto, Tamotsu,Matsuda, Akira,Shuto, Satoshi
, p. 3511 - 3521 (2007/10/03)
The stereoselective hydride reduction of the cis- and trans-substituted cyclopropyl ketones was systematically investigated using a series of structurally simplified substrates, trans-[tertbutyldiphenylsilyloxymethyl]cyclopropyl ketones 1a-e and trans-(benzyloxymethyl)cyclopropyl methyl ketone (2), and the corresponding cis congeners 3a,b,e and 4. The results showed that, not only in the reduction of the cis-substituted cyclopropyl ketones but also in that of the trans-substituted ketones, high stereoselectivity can be realized when the substrate has a bulky substituent on the cyclopropane ring, even though it is attached to the position trans to the acyl moiety. Ab initio calculations based on the density functional theory (DFT) of cyclopropyl ketones showed that (1) the bisected s-cis and s-trans conformers were the only two minimum energy conformers, while the s-cis conformer was more stable than the s-trans and (2) a bulky alkyl group in the acyl moiety and a cis substituent on the cyclopropane ring made the bisected s-cis conformer much more stable. On the basis of these calculations and experimental results, it is likely that the more stable the bisected s-cis conformer of the substrate, the more stereoselective the hydride reduction. Thus, the stereochemistry can be explained by hydride attack on the bisected s-cis conformation of the substrate from the less-hindered face. The predictability of the stereochemical results is predicated on the bisected s-cis transition-state model, which is very important from the viewpoint of synthetic organic chemistry.
Chemical synthesis and biological evaluation of cis- and trans-12,13-cyclopropyl and 12,13-cyclobutyl epothilones and related pyridine side chain analogues
Nicolaou,Namoto,Ritzen,Ulven,Shoji,Li,D'Amico,Liotta,French,Wartmann,Altmann,Giannakakou
, p. 9313 - 9323 (2007/10/03)
The design, chemical synthesis, and biological evaluation of a series of cyclopropyl and cyclobutyl epothilone analogues (3-12, Figure 1) are described. The synthetic strategies toward these epothilones involved a Nozaki - Hiyama - Kishi coupling to form
Synthesis of Optically Active cis- and trans-1,2-Disubstituted Cyclopropane Derivatives by the Simmons-Smith Reaction of Allyl Alcohol Derivatives Derived from (R)-2,3-O-Isopropylideneglyceraldehyde
Morikawa, Tsutomu,Sasaki, Hirofumi,Hanai, Ryo,Shibuya, Akira,Taguchi, Takeo
, p. 97 - 103 (2007/10/02)
The Simmons-Smith reactions of Z- and E-allyl alcohol derivatives 6 derived from (R)-2,3-O-isopropylideneglyceraldehyde (5) were used for the synthesis of optically active cis- and trans-1,2-disubstituted cyclopropane derivatives.Reaction of 6 with diethyl zinc and diiodomethane gave cyclopropane derivatives 7 in 84percent to quantitative yields with 35 to ca. 100percent des.Identical facial selectivities toward the double bonds, 1re-2si for Z-6 and 1re-2re for E-6, were observed in the cyclopropanations.The diastereoselectivity was dependent on the protecting group on the terminal allylic oxygen (R of 6, TBDPS > MOM > Bn) and on the stereochemistry of the double bond (Z > E).For TBDPS ethers Z- and E-6c, cis- and trans-7c were obtained as single diastereomers, respectively.It was clearly demonstrated that the stereoselectivity of the cyclopropanation is controlled by the directing effect of the allylic oxygen (O-1) of the dioxolane ring, which coordinates to the reagent.The terminal allylic oxygen (O-2) lowered the diastereoselectivity.This reaction was applied to the synthesis of optically active cyclopropane analogs of γ-aminobutyric acid (GABA) 18, 22, and ent-22.
