A concise, stereocontrolled total synthesis of rippertenol

The first total synthesis of the unique terpene rippertenol, a molecule with dense stereochemical complexity arrayed on a compact framework largely devoid of functional groups, is described. Key elements include orchestrated and unique applications of aldol condensations, Diels-Alder chemistry, and a ring expansion to advance a chiral starting material containing a single chiral center into the final target in a concise and diastereocontrolled manner.     

A concise stereocontrolled formal total synthesis of (+/-)-podophyllotoxin using sulfoxide chemistry

A short stereoselective formal total synthesis of (+/-)-podophyllotoxin has been carried out from a sulfoxide, using a one-pot tandem conjugate addition/aldol/electrophilic aromatic substitution reaction to form a tetralin, which was converted into picropodophyllin in two steps.     

A stereocontrolled rearrangement of spectinomycin - the stereochemical identity of spectinoic acid

Treatment of N-benayloxycarbonylspectinomycin with weakly acidic catalyses or with bis(tri-n-butyltin)oxide and bromine leads to the formation of a lactone in high yield via a stereocontrolled tertiary α-ketol rearrangement. This product was chemically related to spectionic acid which in turn was transformed into 5-deoxy-α-D-isosacharino-1,4-lactone of known absolute configuration. The stereochemical identity of this acid is thus secured.     

Asymmetric, stereocontrolled total synthesis of paraherquamide A

The first total synthesis of paraherquamide A, a potent anthelmintic agent isolated from various Penicillium sp. with promising activity against drug-resistant intestinal parasites, is reported. Key steps in this asymmetric, stereocontrolled total synthesis include a new enantioselective synthesis of alpha-alkylated-beta-hydroxyproline derivatives to access the substituted proline nucleus and a highly diastereoselective intramolecular S(N)2' cyclization to generate the core bicyclo[2.2.2]diazaoctane ring system.     

A short, concise synthesis of queuine

A short, concise synthesis of queuine was accomplished in a 36% overall yield through a convergent scheme utilizing a reductive amination as the penultimate step. The synthesis demonstrates the utility of silylation to facilitate reactions of various pyrrolo[2,3-d]pyrimidine intermediates, and offers the possibility of easily accessing related pyrrolo[2,3-d]pyrimidines as well as making additional analogues of queuine.     

A stereocontrolled synthesis of delta-trans-tocotrienoloic acid

[reaction: see text] A concise stereoselective total synthesis of a naturally occurring polymerase beta inhibitor, delta-trans-tocotrienoloic acid (2), is described. The key step in the synthesis is an acid-catalyzed cyclodehydration reaction. Additionally, this report corrects a previously reported structural assignment, defines the absolute stereochemistry of 2, and defines key structural requirements for polymerase beta inhibition.     

A simple stereocontrolled synthesis of salinosporamide A

A simple and effective stereocontrolled synthesis of salinosporamide A has been developed. This process, the first synthesis of salinosporamide A, is capable of providing the compound in substantial quantities for further biological studies. Salinosporamide A was of special interest as a synthetic target because of its potent in vitro cytotoxic activity against many tumor cell lines (IC(50) values of 10 nM or less).     

A stereocontrolled synthesis of (+)-saxitoxin

A concise stereoselective total synthesis of (+)-saxitoxin is described. A silver(I)-initiated hydroamination cascade constructs the bicyclic guanidinium ion core from a alkynyl bisguanidine. This sequence creates two C-N bonds, one C-O bond, and three rings and forms a single stereoisomer in a single synthetic transformation. This process enabled us to complete the synthesis of (+)-saxitoxin in 14 steps from N-Boc-l-serine methyl ester.     

A concise, convergent total synthesis of monocerin

A concise and convergent eight-step synthesis of the antifungal metabolite monocerin 1 is reported. The key step involves an allylsilane metathesis/aldehyde condensation sequence to establish the core 2,3,5-trisubstituted tetrahydrofuran. End-game approaches based around intramolecular Heck chemistry revealed an interesting example of formal 6-endo cyclisation, the origin of which was probed using model substrates. The synthesis was ultimately completed by a strategy involving stepwise oxidative cleavage of the C3-ethenyl substituent.     

A concise synthesis of ent-Cholesterol

ent-Cholesterol was synthesized in 16 steps from commercially available (S)-citronellol. The overall yield for the synthesis was 2.0%. This route is amenable to gram-scale preparation of ent-cholesterol. Isotopic incorporation near the end of the synthesis was achieved using labeled methyl iodide. This synthesis is the most practical to date and will make ent-cholesterol more readily available to use as a probe of the function and metabolism of cholesterol.     

A concise synthesis of honokiol

Two approaches to the synthesis of the plant-derived biaryl neolignan honokiol are described. The second approach provided the natural product in either four steps with 34% overall yield or five steps and 55% overall yield.     

A concise synthesis of spirotryprostatin A

The preparation of two new synthons, 2,5- and 2,6-dibromotryptophan esters, and their use in diastereoselective intramolecular N-acyliminium ion spirocyclization methodology for the rapid construction of spirotryprostatin A and analogues are described.     

A concise synthesis of honokiol

A simple synthesis of the natural product honokiol 1 has been developed which proceeds in four steps and provides a 32% overall yield. Suzuki coupling of 4-allyl-2-bromoanisole 3 with 4-hydroxyphenyl boronic acid, followed by allylation, gave 5-allyl-4′-allyloxy-2-methoxy-biphenyl 5. This compound 5 underwent Lewis acid-catalyzed Claisen rearrangement and demethylation in a one-pot reaction which yielded honokiol.     

A concise synthesis of denbinobin

A concise synthesis of denbinobin is described via an intramolecular free radical cyclization and Fremy’s salt mediated oxidation as a key reactions. A seven-step process starting from commercially available 3,5-dimethoxybenzyl bromide (6) and 2-bromoisovanillin (5) effectively constructs the natural product denbinobin (1).     

A concise synthesis of beta-asparaginyladenylate

Stable analogues of acyladenylate intermediates, such as N-acylphosphoramidates, are useful probes of tRNA aminoacylation and enzyme mechanism, and have potential application as enzyme inhibitors. We now report a concise, "one-pot" synthesis of beta-asparaginyladenylate using a novel coupling protocol that yields the target N-acylphosphoramidate in three reactions from readily available precursors. This simple synthetic procedure may represent a general approach for the preparation of functionalized N-acylphosphoramidates from amides that do not undergo coupling under the conditions of existing literature protocols.     

A concise synthesis of butylcycloheptylprodigiosin

A short and efficient total synthesis of the tripyrrole alkaloid butylcycloheptylprodigiosin is described. Key to the brevity of the approach is a two-step synthesis of macrocyclic formylpyrrole 4 from cyclononenone 6.     

A highly stereocontrolled total synthesis of dysiherbaine

A total synthesis of dysiherbaine, a potent agonist of AMPA-KA type glutamate receptors, has been accomplished in completely stereocontrolled manner starting from tri-O-acetyl-D-galactal in 25 steps and in 3% overall yield.     

A concise,asymmetric synthesis of tetramic acid derivatives

[reaction: see text] A simple, asymmetric synthesis of tetramic acid derivatives is described in this paper. The key step is a carbonyl transfer from carbonyldiimidazole (CDI) to alpha-diimines (I) to form N-alkyl-4-alkylamino-5-methylenepyrrol-2-ones (II). In turn, these compounds can be easily transformed into tetramic acid derivatives (III) in two additional steps.     

A concise total synthesis of DL-histrionicotoxin

The synthesis of (+/-)-histrionicotoxin has been achieved in just nine steps using a two-directional synthesis strategy. Key reactions include a two-directional cross-metathesis, a tandem oxime formation/Michael addition/1,4-prototopic shift/[3 + 2]-cycloaddition cascade, a selective Z,Z-bisenyne formation, and a one-pot N-O and bischloroacetylene reduction.