Wei-Min Dai

Designed Enediynes: A New Class of DNA-Cleaving Molecules with Potent and Selective Anticancer Activity

The rational design and biological actions of a new class of DNA-cleaving molecules with potent and selective anticancer activity are reported. These relatively simple enediyne-type compounds were designed from basic chemical principles to mimic the actions of the rather complex naturally occurring enediyne anticancer antibiotics, particularly dynemicin A. Equipped with locking and triggering devices, these compounds damage DNA in vitro and in vivo on activation by chemical or biological means. Their damaging effects are mainfested in potent anticancer activity with remarkable selectivities. Their mechanism of action reactive benzenoid diradicals that cause severe DNA damage. The results of these studies demonstrate the potential of these de novo designed molecules as biotechnology tools and anticancer agents.

Generation of an Aromatic Amide-Derived Phosphane (Aphos) Library by Self-Assisted Molecular Editing and Applications of Aphos in Room-Temperature Suzuki–Miyaura Reactions

Aromatic amide-derived phosphanes (Aphos) are hemilabile P,O-coordinating ligands, which, when combined with a Pd precursor, yield a promising precatalyst system for Suzuki-Miyaura cross-coupling reactions. A focused library of Aphos ligands has been constructed for structural optimization, with the target of improving catalytic efficacy. By using microwave irradiation at accurately regulated temperature, an expeditious and reproducible one-pot synthesis and screening protocol was designed and experimentally validated. The success is based on a unique self-assisted molecular editing (SAME) process in which both the substrate and the product molecules catalyze formation of the product. Thus, starting from a 4-chlorobenzamide-derived Aphos as the substrate, parallel reactions with a selected set of arylboronic acids, in the absence of an added external phosphane ligand to Pd, produced a family of structurally edited Aphos ligands. The resultant reaction mixture containing the new Aphos, the Pd species, and the base could be used for in situ screening of the Aphos efficacy in a reference Suzuki-Miyaura coupling reaction. The structures of all Aphos ligands were characterized by 31P NMR spectroscopy and their catalytic profiles in the reference reaction were evaluated by HPLC analysis. These data allowed the identification of an efficient Aphos ligand, capable of promoting room-temperature Suzuki-Miyaura coupling of unactivated and sterically hindered aryl chlorides with arylboronic acids under mildly basic conditions.

Chiral ligands derived from abrine. Part 6: Importance of a bulky N-alkyl group in indole-containing chiral beta-tertiary amino alcohols for controlling enantioselectivity in addition of diethylzinc toward aldehydes

A number of chiral beta-amino alcohols possessing a 3-indolylmethyl group have been synthesized from the alkaloid (S)-abrine and elucidated for potency in the catalytic enantioselective ethylation of PhCHO with Et2Zn. In general, the secondary amines 15a-d bearing a dialkylhydroxymethyl group induced (R)-1-phenyl-1-propanol, whereas 15e-g and 18 bearing a diarylhydroxymethyl group favored the (S)-enantiomer. In contrast, the beta-tertiary amino alcohols 20b d and 21 produced (R)-1-phenyl-1-propanol. regardless of the substituents at the carbon bearing the hydroxy group. Enantiomeric excess of 87.5% was obtained for (R)-1-phenyl-1-propanol using ligand 21 as the promoter. Eleven substituted benzaldehydes and naphth-aldehydes were examined for enantioselective ethylation by using 21 and the chiral alcohols were obtained in 93-97% ee, except for o-BrC6H4CHO and p-Me2NC6H4CHO. Excellent enantioselectivity was also observed in the ethylation of cyclohexanecarboxaldehyde (94.8% ee) and 2-thiophenecarboxaldehyde (94.9% ee) by using catalytic 21. The anti 5/4/4-fused tricyclic TS I was proposed to rationalize the asymmetric induction. The diethylhydroxymethyl and N-2-t-butylethyl groups are believed to enforce the preference for the anti-TS(R) I and it results in high enantioselectivity

Chemistry of aminophenols. Part 1: Remarkable additive effect on Sonogashira cross-coupling of 2-carboxamidoaryl triflates and application to novel synthesis of indoles

A novel and general synthesis of indoles has been established by utilizing 2-aminophenols as the starting materials. The key step is a modified Pd(0)–Cu(I)-catalyzed cross-coupling of 1-alkynes with 2-carboxamidoaryl triflates in the presence of n-Bu4NI as the additive. The 2-alkynylanilides obtained were subjected to an alkoxide-mediated cyclization to provide a number of indole containing compounds possessing substituents at the C2, C4, C5, and/or C6 position(s) in good overall yields.

Chemistry of aminophenols. Part 3: First synthesis of nitrobenzo[b]furans via a coupling-cyclization approach

Abstract The first synthesis of 4-, 5-, and 6-nitrobenzo[b]furans has been achieved via the Sonogashira cross-coupling reaction of 2-iodonitrophenol acetates prepared from commercially available and inexpensive 2-aminonitrophenols. The obtained 2-alkynylnitrophenol acetates were subjected to a KOtBu-promoted cyclization at room temperature to form nitrobenzo[b]furans. Examples of the synthesis of other substituted benzo[b]furans and the one-pot coupling–cyclization are given.

Recent progress in asymmetric synthesis of pyrrolizidines

Asymmetric syntheses of optically active pyrrolizidines are reviewed according to the chiral pools used

Chemistry of aminophenols. Part 2: A general and efficient synthesis of indoles possessing a nitrogen substituent at the C4, C5, C6, and C7 positions

A general and efficient synthesis of indoles possessing a nitrogen substituent at the C4, C5, C6, and C7 positions has been developed. Starting from commercially available nitro 2-aminophenols, 5-, 6-, and 7-arenesulfamoylindoles were synthesized via a base-promoted ring closure of 2-alkynylanilides, reduction of the nitro group, and sulfonylation. C4 nitrogen substituted indoles were synthesized from 2-chloro-1,3-dinitrobenzene via cyclization of 2-alkynyl-1,3-diaminobenzene as the key step.

Asymmetric Wittig reactions of chiral arsonium ylides. Part 3: Reversal of stereochemistry caused by metal cation in enantioselective olefination of 4-substituted cyclohexanones using a C2-symmetric chiral arsine

Abstract A novel C2-symmetric chiral arsine was synthesized from (S)-(−)-1,1′-bi-2-naphthol in three steps. It was employed in the enantioselective olefination of 4-substituted cyclohexanones via a stabilized ylide formed in situ from the corresponding arsonium salt. Enantioselectivity up to 40% was obtained. Moreover, a reversal in the stereochemistry of the product was observed simply by changing the counter cation of the base from lithium to potassium.

A Concise Total Synthesis of Amphidinolide T2

RCM + AD = T2: In the presence of the C16-methylene group, regioselective ring-closing metathesis (RCM) formed the (12E)-endocyclic double bond, which underwent Os-catalyzed asymmetric dihydroxylation (AD) to give the desired 12,13-diol intermediate required for the total synthesis of amphidinolide T2 in 16 linear steps in 8.0% overall yield.

Chiral ligands derived from Abrine .2. Oxazolidines as promoters for enantioselective addition of diethylzinc toward aromatic aldehydes

A number of indole-containing chiral oxazolidines 2a-i have been synthesized from Abrine readily available from the seeds of Abrus precatorius. Catalysis of these oxazolidines for the addition of diethylzinc toward benzaldehyde was examined. A significant role of the substituent(s) in the catalyst on the degree of asymmetric induction was noted. Moderate enantioselectivity up to 59.8% was recorded. Copyright (C) 1996 Published by Elsevier Science Ltd