Total synthesis of (+/-)fasicularin via a 2-amidoacrolein cycloaddition

The total synthesis of the cytotoxin fasicularin is described. The key steps include the following: (1) an intermolecular Diels-Alder cycloaddition of a 2-(triflamido)acrolein with the dioxolane ketal of trideca-1,3-dien-7-one to establish the trans-perhydroisoquinoline stereochemistry, (2) a stereoelectronically controlled hydride addition to a N(1)-C(2) iminium ion to introduce the equatorial hexyl substituent, and (3) elaboration of the pyrido ring by an internal aldol reaction.     

Total synthesis of the sesquiterpene (+/-)-illudin C via an intramolecular nitrile oxide cycloaddition

[reaction: see text] A convergent total synthesis of illudin C is described. The tricyclic ring system of the natural product was quickly assembled from cyclopropane and cyclopentene precursors via a novel oxime dianion coupling reaction and a subsequent intramolecular nitrile oxide-olefin cycloaddition.     

Total syntheses of (+/-)-montanin A and (+/-)-teuscorolide

The first total syntheses of (+/-)-montanin A and (+/-)-teuscorolide have been achieved from an advanced precursor previously developed via a Diels-Alder strategy; in the synthetic sequence, the synthesis of montanin A was first accomplished in 8 steps, from which teuscorolide was readily achieved in 2 steps by using a novel furan oxidative cyclization-retro-cyclization process as a key operation.     

Total syntheses of (+/-)-anchinopeptolide D and (+/-)-cycloanchinopeptolide D

The first synthesis of (+/-)-anchinopeptolide D (4) has been accomplished in seven steps in 10% overall yield from octopamine hydrochloride (17), N-(Boc)glycine (16), and 5-amino-2-hydroxypentanoic acid (22). The key step is the aldol dimerization and hemiaminal formation of alpha-keto amide 26, which gives primarily protected anchinopeptolide D 27 under kinetically controlled conditions. Cycloanchinopeptolide D (31) has been prepared by the unprecedented head-to-head photodimerization of the two hydroxystyrylamides of 4 using the hydrophobic effect in water to force the two side chains into close proximity so that [2 + 2] cycloaddition is faster than trans to cis double bond isomerization. Coupling of amine 21 with pyroglutamic acid affords the naturally occurring tripeptide 35, which had been assigned glutamic acid structure 34.     

Total syntheses of (+/-)-crinine, (+/-)-crinamine, and (+/-)-6a-epi-crinamine via the regioselective synthesis and Diels-Alder reaction of 3-aryl-5-bromo-2-pyrone

We have devised a new unified synthetic protocol to (+/-)-crinine, (+/-)-crinamine, and (+/-)-6a- epi-crinamine from the Diels-Alder cycloadduct of 3-(3,4-methylenedioxyphenyl)-5-bromo-2-pyrone with TBS vinyl ether. The requisite 3-(3,4-methylenedioxyphenyl)-5-bromo-2-pyrone was prepared from the C3-selective Stille coupling reaction of 3,5-dibromo-2-pyrone. Also noted is that the vinyl bromide can be used as a handle for further derivatization.     

Total synthesis of (+/-)-alantrypinone by hetero Diels-Alder reaction

An efficient total synthesis of (+/-)-alantrypinone 4 by hetero Diels-Alder reaction of a novel pyrazine diene 9 with either a functionalized 3-alkylideneoxindole or 3-methyleneoxindole itself is described. The Diels-Alder reactions provide both the desired regiochemistry and exo selectivity. An interesting anionic equilibration between alantrypinone 4 and its epimer 31 or between its ester analogues 23 and 24 has been demonstrated, and a mechanism has been proposed.     

Stereoselective syntheses of (+/-)-komaroviquinone and (+/-)-faveline methyl ether through intramolecular Heck reaction

[reaction: see text] An efficient, flexible, and stereoselective convergent route for constructing the trans-10-hydroxy-1,1-dimethyloctahydrodibenzo[a,d]cyclohepten-7-ones (5a-c) was achieved via intramolecular Heck reaction. This strategy has been successfully implemented for the syntheses of (+/-)-komaroviquinone (3) through (+/-)-coulterone dimethyl ether (5c) and (+/-)-faveline methyl ether (1a).     

A concise total synthesis of (+/-)-bakkenolide A by means of an intramolecular Diels-Alder reaction

(+/-)-Bakkenolide A was prepared in five steps from ethyl 4-benzyloxyacetoacetate by sequential alkylations with tiglyl bromide nd cis-5-bromo-1,3-pentadiene, followed by an intramolecular Diels-Alder reaction as the key step. The known 7-epibakkenolide A and novel 10-epi- and 7,10-diepibakkenolide A stereoisomers were obtained as minor byproducts.     

Total syntheses of (+/-)-preussomerins G and I

[formula: see text] Preussomerins G and I (2 and 3) have been synthesized for the first time. The key reaction in the synthesis is a possibly biomimetic tautomerization reaction depicted in Scheme 3 and the foregoing graphic. The driving force for this interesting rearrangement is primarily derived from the increase in resonance energy associated with converting a naphthalene ring into two isolated benzene rings.     

Total synthesis of (+/-)-8alpha-hydroxystreptazolone

[reaction: see text] The intramolecular Pauson-Khand reaction of 2-oxazolone derivatives with a suitable pentynyl appendage exclusively gave the corresponding 4-hydroxy-6-substituted-9-oxa-1-azatricyclo[6.2.1.0(5,11)]undec-5-en-7,10-diones. Based on this newly developed Pauson-Khand reaction of 2-oxazolone-alkyne derivatives, the first total synthesis of (+/-)-8alpha-hydroxystreptazolone was accomplished in a highly stereoselective manner.     

2-(N-Allylaminomethyl)cinnamaldehydes as substrates for syntheses of aza-polycycles via intramolecular cycloaddition reactions

Syntheses of a variety of aza-polycycles employing 2-(N-allylaminomethyl)cinnamaldehydes derived from Morita–Baylis–Hillman adducts of acrylates via intramolecular 1,3-dipolar cycloaddition, or Aza-Diels–Alder or domino Knoevenagel/hetero Diels–Alder cycloaddition reactions are described. Whereas the Aza-Diels–Alder afforded a mixture of cis- and trans-isomers of substituted 1,2,3,4,4a,5,10,10a-octahydrobenzo[b][1,6]naphthyridines, the 1,3-dipolar cycloaddition and domino Knoevenagel/hetero Diels–Alder were diastereoselective to produce exclusively cis-derivatives of 1,2,3,4,4a,6,7,8,9,9a-decahydro-1H-pyrido[3,4-b]pyrrolizine-8a-carboxylates and 3,4,4a,5,7,8,9,10b-octahydro-1H-chromeno[3,4-c]pyridin-10(2H)-ones, respectively.     

Formal syntheses of (+/-)-pinnaic acid and (+/-)-halichlorine

[chemical reaction: see text]. Concise formal syntheses of marine alkaloids (+/-)-pinnaic acid (1) and (+/-)-halichlorine (2) have been accomplished from a common intermediate. The syntheses illustrate the utility of selective olefin cross metathesis methodologies for the elaboration of advanced synthetic intermediates in complex molecule synthesis.     

Total synthesis of (+/-)-stenine using the IMDAF cycloaddition of a 2-methylthio-5-amido-substituted furan

[reaction: see text]. The intramolecular [4 + 2]-cycloaddition of a 2-methylthio-5-amidofuran was used to create the azepinoindole skeleton present in the Stemona alkaloid stenine. The rearranged cycloadduct was converted to stenine (1) in 11 additional steps via a sequence that features a Crabtree catalyst directed hydrogenation (9-->10), iodolactonization (2-->11), and a Keck allylation (11-->12).     

Total syntheses of (+/-)-cis-trikentrin A and (+/-)-cis-trikentrin B via electrocyclic ring closures of 2,3-divinylpyrrolines

[Structure: see text] A convergent and versatile strategy for the diastereoselective syntheses of (+/-)-cis-trikentrin A and B in 10 and 12 steps, respectively, from commercially available N-BOC-2-pyrrolidinone is described. The key step in each of the total syntheses is the construction of the central benzene ring via a facile 6pi-electrocyclic ring closure of an appropriately substituted 2,3-divinylpyrroline, in turn, readily available by a Stille coupling reaction.     

First total syntheses of (+/-)-annuionone B and (+/-)-tanarifuranonol

The intramolecular Diels-Alder reaction of o-quinol allyl ether was accomplished and subsequently applied to the first total syntheses of natural products annuionone B (1) and both the proposed and revised structure of tanarifuranonol, 4 and 17.