Formal synthesis of (±)-perhydrohistrionicotoxin via a stepwise [3+3] annelation strategy

A formal synthesis of (±)-perhydrohistrionicotoxin is described that includes a highly diastereoselective modified Sharpless aziridination and a stepwise [3+3] annelation reaction for the stereoselective construction of the key spiropiperidine motif.     

A novel synthetic route for the total synthesis of (±)-uleine

In this study, a new synthetic route for the total synthesis of (±)-uleine is described. The important step in the synthesis of this alkaloid consists of an intramolecular cyclization of the D ring of the azocino[4,3-b]indole skeleton. Reduction of (N-methyl){3-β-ethyl-4-oxo-2,3,4,9-tetrahydrospiro[1H-carbazole-1,2′(1,3)dithiolane]-2-yl}-2-acetamide with borane yielded the corresponding (N-methyl){3-β-ethyl-4-hydroxy-2,3,4,9-tetrahydrospiro[1H-carbazole-1,2′(1,3)dithiolane]-2-yl}-2-acetamide, which underwent acid-catalyzed ring closure to produce azocino[4,3-b]indole core. Finally, the synthesis of (±)-uleine was completed through several steps from the azocino[4,3-b]indole core.     

The biomimetic synthesis of SNF4435C and SNF4435D, and the total synthesis of the polyene metabolites aureothin, N-acetyl-aureothamine and spectinabilin

Full details of the biomimetic conversion of polyene metabolite spectinabilin (5) into the isomeric natural products SNF4435C (1) and SNF4435D (2) by a cascade of E/Z-isomerizations and electrocyclizations are reported. Additionally, short total syntheses of the related natural products (±)-aureothin (3), (±)-N-acetyl-aureothamine (4) and (±)-spectinabilin (5) are presented. The key steps in the synthesis of (±)-3, (±)-4 and (±)-5 are the construction of the tetrahydrofuran motif using a palladium-catalyzed cycloaddition and the ruthenium-catalyzed cross metathesis of alkene 17 to form the common intermediate, boronic ester 24, which was further transformed using a trans-selective Suzuki coupling with a dibromide and a stereospecific Negishi-type methylation.     

Total synthesis of (±)-γ-lycorane via the electrocyclic ring closure of a divinylpyrroline

A concise total synthesis of (±)-γ-lycorane is described. The key step in the synthesis is the 6π-electrocyclic ring closure of a divinylpyrroline to give a tetrahydroindole, which is subsequently hydrogenated to give the all-cis indolizidine core.     

Total synthesis of (±)-cyclooroidin

The first total synthesis of (±)-cyclooroidin, a member of the pyrrole-imidazole alkaloid family recently isolated from the sponge Agelas oroides in optically pure form, is described. The synthesis was achieved in nine linear steps, with an overall yield of 10%. Key step was a Wolff bromoketone synthesis performed on the intermediate longamide B.     

Synthesis of cylindricine C and a formal synthesis of cylindricine A

This paper reports the synthesis of the alkaloid natural product (±)-cylindricine C, in addition to a formal synthesis of (±)-cylindricine A. The key step in our sequence is the (ipso) regioselective addition of an alkyl Grignard reagent to a C-2 substituted pyridinium salt to generate the dihydropyridone core of the alkaloid targets. After cyclisation to form the A and C rings of the cyclindricines the net outcome is a short (13 steps) synthesis of this natural product.     

Regioselective reduction of N-alkyl-3-sulfonyl glutarimides to δ-lactams. Formal synthesis of (±)-paroxetine and (±)-tacamonine

A convenient method for the preparation of 4- or 5-substituted 3-sulfonyl-δ-lactams via regioselective reduction of N-alkyl-3-sulfonyl glutarimides is described. Formal synthesis of (±)-paroxetine and (±)-tacamonine is also reported.     

Total synthesis of (±)-antofine

An efficient preparation of (±)-antofine is described. The main steps involved in this synthesis are the Horner–Wadsworth–Emmons reaction, the intramolecular Schmidt reaction of an azido aldehyde, and the one-pot deprotection of the N-formyl group, followed by Pictet–Spengler cyclization. The asymmetric hydrogenation of the trisubstituted α,β-unsaturated ester is also explored, however only moderate enantio-control (55% ee) is obtained. Finally, (±)-antofine is prepared in six steps from the phenanthryl aldehyde 5 with an overall yield of 35%.     

Efficient construction of novel α-keto spiro ketal and the total synthesis of (±)-terreinol

The first total synthesis of (±)-terreinol is described. An intramolecular Pd(II)-catalyzed cycloisomerization of a 2-(1′-alkynyl)benzyl alcohol via an apparent 6-endo diagonal pathway led to the 1H-isochromene ring system, which was further converted to the desired spiro ketal via an iodine-mediated intramolecular spiro-cyclization.     

A formal synthesis of (±)-physostigmine via 3,3-rearrangement of a bis-enamine

A new flexible approach to hexahydropyrrolo[2,3-b]indole system via the [3,3]-sigmatropic rearrangement of 1-(2′-methoxycarbonyl-N-methylvinylamino)skatole, culminating in the synthesis of (±)-desoxyeseroline, is described.     

Total synthesis of (±)-lantalucratins A and B by CAN-mediated oxidative cyclization

The first total synthesis of (±)-lantalucratins A and B is described. Introduction of an alkyl side chain at the 6-position was proceeded by directed ortho-lithiation and subsequent alkylation reaction to afford 6-alkyl-5,7,8-trimethoxy-1-naphthol as a synthetically important intermediate for (±)-lantalucratins A and B in excellent yield with complete regioselectivity. The 1,2-naphthoquinone fused five-membered cyclic ether framework was constructed directly from 3-hydroxyalkyl-naphthalenes by oxidative intramolecular cyclization reaction with diammonium cerium(IV) nitrate. (±)-Lantalucratins A and B were obtained in 69% and 45% overall yields, respectively.     

Total synthesis of (±)-protoemetinol

A new approach to the benzo[a]quinolizidine alkaloid was described. Total synthesis of (±)-protoemetinol (1) was reported.     

Anodic cyanation of C-4 hydroxylated piperidines: total synthesis of (±)-alkaloid 241D

A stereospecific synthesis of dendrobates (±)-alkaloid 241D is described. Key steps in this approach involved the stepwise electrochemical synthesis of C-4 substituted α-aminonitriles and their alkylation with iodomethane and 1-bromononane, respectively. The N-aryl group was removed in the last step through a Birch dearomatization followed by the hydrolysis of the intermediate dienamines.     

A variation of the Pictet-Spengler reaction via a sequential reduction-cyclization reaction of N-acylcarbamates: synthesis of 1-substituted tetrahydroisoquinoline derivatives

A new variation of the Pictet-Spengler reaction for the synthesis of 1-substituted tetrahydroisoquinoline derivatives has been developed. The reaction employs the reduction of N-acylcarbamates by DIBAL-H followed by simultaneous cyclization mediated by BF₃·OEt₂. The synthetic potential of this method has been illustrated by the synthesis of the tetrahydroisoquinoline alkaloids, (±)-xylopinine, (±)-laudanosine, (±)-8-oxo-O-methylbharatamine, and (±)-isoindoloisoquinolone.     

Total synthesis of (±)-xanthocidin using FeCl3-mediated Nazarov reaction

The total synthesis of the antibiotic, (±)-xanthocidin (1), is described. The FeCl₃-promoted fast Nazarov reaction of the β-alkoxy divinyl ketone in the presence of t-BuOH provided the α-exo-methylene cyclopentenone, which is the core skeleton of this natural product. After methoxymethyl (MOM) esterification and protection of the reactive exo-methylene unit with a phenylseleno group, dihydroxylation, followed by oxidation, gave xanthocidin MOM ester. Finally, this ester was converted into (±)-xanthocidin (1) under mild conditions.     

An efficient synthesis of novel deoxy phospha sugar pyrimidine nucleosides

An efficient method is described in the synthesis of several novel deoxy phospha sugar pyrimidine nucleosides in racemic form, analogs of normal sugar nucleosides, in high yields by treatment of (±)-2-aminophospholane 1-oxide with several, α-cyano-, -acetyl-, -ethoxycarbonyl-β-ethoxy-N-ethoxycarbonylacrylamides.     

Alkaloid synthesis using 2nd generation palladium-catalyzed cycloalkenylation. Diastereoselective total synthesis of α-skytanthine

An efficient approach to the synthesis of 3-azabicyclo[3.3.0]octanes and 3-azabicyclo[4.3.0]nonanes by 2nd generation palladium-catalyzed cycloalkenylation is described. Additionally, this reaction is used for the diastereoselective total synthesis of (±)-α-skytanthine.     

Substrate scope in the direct imine acylation of ortho-substituted benzoic acid derivatives: the total synthesis (±)-cavidine

The direct imine acylation (DIA) and subsequent cyclisation of a range of imines with ortho-substituted benzoic acid derivatives is described. Variation in the coupling reagents, imine and benzoic acid were all examined. The DIA procedure was also applied in the total synthesis of (±)-cavidine.     

Total synthesis of (±)-brazilin and formal synthesis of (±)-brazilein, (±)-brazilide A using m-CPBA

Total synthesis of (±)-brazilin has been accomplished. m-CPBA epoxidation of allyl alcohol 10 and epoxy opening reaction mediated by m-chlorobenzoic acid, formed in situ as a byproduct, gave advanced intermediate diol 14. O-alkylation and cyclization gave phenol 6 which enabled the formal synthesis of (±)-brazilein and (±)-brazilide A.     

A conjugate addition/dipolar-cycloaddition cascade sequence for the synthesis of (±)-cylindricine C

An efficient stereocontrolled route to (±)-cylindricine C is described. Reaction of 9-hydroxynon-1-en-5-one oxime with 2,3-bis(phenylsulfonyl)-1,3-butadiene affords a 7-oxa-1-azanorbornane cycloadduct in high yield. The formation of the bicyclic isoxazolidine arises from conjugate addition of the oxime onto the diene to give a transient nitrone that spontaneously undergoes an intramolecular dipolar cycloaddition. The resulting cycloadduct derived from the cascade sequence was converted into (±)-cylindricine C by: (1) a reductive-cyclization to set the BC-ring skeleton, (2) a base-induced cyclization to construct the tricyclic core, and (3) an oxidation-conjugate addition of the n-hexyl side chain to complete the synthesis.