A Concise, Enantioselective Synthesis of (-)- and (+)-Hongconin

Optically pure enone 9c, available in three steps from known 6-deoxy D-galactal derivative 7b, reacts with cyanophthalide 6 to directly afford the natural product (-)-hongconin (1), a compound from traditional Chinese medicine recently shown to exhibit antianginal activity. The enantiomer of 1 and its (+)-cis-diastereomer were also synthesized in a parallel fashion from the L-sugar counterpart. The use of C-glycoside Michael acceptors, as opposed to their O-glycoside counterparts, represents a potentially useful simplification of phthalide annulation methodology in synthesizing numerous other such optically pure isochromanquinoids, since it obviates the inconvenience of additional steps late in the synthetic scheme associated with reductive manipulation of a remaining acetal moiety into the desired pyran ring substituent.     

The Total Synthesis of (±)-Isocomene by an Intramolecular Ene Reaction. Preliminary communication

The racemic sesquiterpene isocomene ( 1 ) has been synthesized starting from 1,7-octadien-3-one ( 2 ) in a stereoselective manner (Scheme 2). In the key step 4 → 5 the C(7), C(8)-bond was formed by an intramolecular thermal ene reaction. Further elaboration of 5 involved the ring contraction 6 → 7 , the elimination 8 → 9 and the final olefin isomerization 9 → 1 .     

Total Synthesis of (-)- and (+)-Balanol(1)

Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described. In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-epsilon-caprolactam. Resolution prior to coupling to the benzophenone subunit provided access to both enantiomers of balanol. In the second approach, an efficient silicon-mediated cyclization of (2S,3R)-3-hydroxylysine followed by reduction provided the azepane subunit in enantiomerically pure form. The sterically congested benzophenone subunit was assembled from two highly substituted aromatic precursors by way of an anionic homo-Fries rearrangement.     

Total Synthesis of (±)-Lysergic Acid by an Intramolecular Imino-Diels-Alder Reaction. Preliminary communication

(±)-Lysergic acid ( 1 ) has been synthesized from 4-hydroxymethyl-1-tosylindole ( 2 ) by a sequence of 9 steps. The crucial thermolysis 9 → 10 involves the in situ-generation of the transient diene III which undergoes an intramolecular cycloaddition to a C, N-double bond at 200° and at low stationary concentration of III.     

Stereoselective Synthesis of (Z)-1-Benzhydryl-4-cinnamylpiperazines via the Wittig Reaction

A synthetic method of producing (E)- and (Z)-isomers of 1-benzhydryl-4-cinnamylpiperazines in a specific ratio from corresponding benzhydrylpiperazine is described. Of the three compounds synthesized (5a–c), the ratio of E/Z-isomers remained around 15:85. The key intermediates, 1-benzhydryl-4-(2,2-dimethoxyethyl)piperazine derivatives (3a–c), were prepared by nucleophilic substitution reaction of benzhydrylpiperazines (2a–c) with chloroacetaldehyde dimethylacetal in good yield (up to 88%). Hydrolysis of 3a–c gave the corresponding aldehydes 4a–c, which when subjected to the Wittig reaction followed by column purification to afford 1a–c (E-isomers) and 6a–c (Z-isomers) in pure form. The isolated compounds were characterized by NMR and mass spectral analysis.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

A Facile Synthesis of 1(3)-Acylglycerols

A facile route is described for the synthesis of 1(3)-acylgiycerols for the first time through hydroxylation of allyl esters of fatty acids with the novel reagent cety1trimethy1ammonium permanganate in a non-aqueous medium.     

Total Synthesis of (-)-Muscoride A

The recently isolated cyanobacterium metabolite muscoride A was synthesized in 15 steps and in 4.3% overall yield. Novel structural features of this peptide antibiotic include the presence of a threonine-derived bioxazole core and an N-(1,1-dimethyl)allyl ("reverse prenyl") valine residue. In the context of our synthesis, efficient new strategies for the preparation of these segments were developed. The synthesis of two epimers of muscoride A allowed the unambiguous assignment of the relative and absolute configuration of the natural product by NMR and optical rotation analyses.     

Total Synthesis of Everninomicin 13,384-1-Part 1: Synthesis of the A(1)B(A)C Fragment

The powerful antibiotic everninomicin 13,384-1 (1, Ziracin) has been prepared for the first time through a total synthesis. The 1-->1'-disaccharide and the two orthoesters of this target molecule were introduced by new methodologies using a tin acetal and 1,2-phenylseleno migrations. The reaction sequence also relies on stereoselective glycosidations and subtle manipulations of protecting groups. In addition to the introduction of new synthetic methodologies, this total synthesis should allow the preparation of combinatorial libraries of semisynthetic analogues of this highly promising antibiotic for biological screening purposes.     

A Facile Synthesis of Thioacids by Hydrolysis of 1-(Acylthio)ethaniminium Chlorides

A facile method for the preparation of thioacids in moderate to good yields has been developed by hydrolysis of 1-(acylthio)ethaniminium chlorides under a liquid-liquid two phase system consisting of benzene and a sodium hydroxide aqueous solution at room temperature. We have achieved facile preparation of these compounds without use of toxic compounds such as hydrogen sulfide.     

A Formal Total Synthesis of (-)-Brevisamide

A formal total synthesis of (−)-brevisamide has been achieved. The synthetic approach highlights a chemoselective asymmetric dihydroxylation and a one-pot Fraser-Reid epoxidation/PMB protection reaction sequence.     

A Facile Synthesis of Aldehyde and Ketone via Senochemical Barbier Reaction and Oxidation

Methyl ketone is prepared by a sonochemical Barbier reaction of methyl iodide, magnesium powder and aldehyde in Benzene/THF (9/1) solvent in a commercial ultrasonic cleaning bath (39 kHz), followed by the addition of N-chlorosuccinimide (NCS) as an oxidizing agent.     

A Facile One-Pot Synthesis of 4-Acyl and 4-(1-Hydroxyethyl)Sydnones

A series of 4-formyl-, 4-acetyl- and 4-(l'-hydroxyethyl)sydnones have been prepared in good yields by reaction of sydnone with butyllithium or a Grignard reagent and N,N-dimethylformamide, N,N-dimethylacetamide and acetylaldehyde, respectively.     

Total Synthesis of (+)-7-epi-Tarchonanthuslactone via a Chelation-Controlled Mukaiyama Aldol Reaction

An asymmetric total synthesis of (+)-7-epi-tarchonanthuslactone was achieved from commercially available methyl (R)-3-hydroxybutyrate. The key step employed a diastereoselective chelation-controlled Mukaiyama aldol reaction to construct the chiral hydroxyl group at the C-5 position.     

Facile Synthesis of Enantiomerically Pure 1-（5-Bromo-2-chlorophenyl）-1-（4-ethoxyphenyl）ethane

A facile 7-step procedure for the synthesis of enantiomerically pure 1-（5-bromo-2-chlorophenyl）-1-（4-ethoxyphenyl）ethanes[（R）-2 and（S）-2] that started from （5-bromo-2-chlorophenyl）（4-ethoxyphenyl）methanone 3 was developed.The key step was the resolution of 2-（5-bromo-2-chlorophenyl）-2-（4-ethoxyphenyl）acetic acid 6 by crystallizations of its L-and D-menthyl esters 7 and 8 from petroleum ether to give optically pure enantiomers 9 and 10,respectively.The absolute configurations of the products were unambiguously determined by single-crystal X-ray diffractions of four key intermediates,9,10,13 and 14.This procedure is characterized by inexpensiveness,scalability and ability to produce two individual enantiomers of a diarylethane with unambiguously determined absolute configurations and high enantiomeric purities.     

A New Enantioselective Total Synthesis of Natural Vincamine via an Intramolecular Mannich Reaction of an Silyl Enol Ether

Natural Vincamine ( 1 ) has been synthesized in an enantioselective manner starting from the ethylpentenal 7 . In the key step a mixture of the diastereoisomeric racemates, 14 and 15 , was directly obtained from the silyl enol ether 11 and the dihydro-β-carboline 12 by the way of an intramolecular Mannich reaction of the intermediate 13 (Scheme 4). The undesired stereoisomers, 14 and 15b , were recycled to 15a using the related reversible Mannich reaction 18 ? 14 + 15 , followed by crystallization of the salt from 15a and (+)malic acid. 15a was converted to natural vincamine ( 1 ) in several steps including the known transformation 20→1 .