Total synthesis of (+/-)-terpestacin and (+/-)-11-epi-terpestacin

The total synthesis of racemic terpestacin and 11-epi-terpestacin using the allene ether Nazarov reaction as the key step is described. All stereochemistry is derived from the stereogenic carbon atom that is formed during the Nazarov reaction.     

Total synthesis of (+/-) tanikolide

The natural polyketide (+/-)-tanikolide (1) was prepared in eight steps starting from hex-5-enol. Key steps in this synthesis are a Sharpless dihydroxylation and a Grignard reaction between an alkyl halogenide and a ketone. The lactonization occurred spontaneously during the oxidation of the primary alcohol function to the carboxy group.     

Total synthesis of (+/-)-mersicarpine

The first total synthesis of the indole alkaloid mersicarpine is reported. Key steps include a beta-dicarbonyl radical cyclization, as well as an oxidation of the benzopyrrole moiety to establish the masked 1,2-dicarbonyl functionality. An X-ray crystal structure and discussion of the 1H NMR behavior of the natural product are also presented.     

Total synthesis of (+/-)-morphine

[Structure: see text] The morphinan skeleton was effectively synthesized by an intramolecular Mannich-type reaction. Further transformation led to total synthesis of morphine.     

Total synthesis of (+/-)-perophoramidine

The first total synthesis of racemic perophoramidine is described. The key step features the highly stereoselective introduction of the vicinial quaternary centers via base-promoted carbon-carbon bond formation between a 3-alkylindole and a 3-bromo-3-alkylindolin-2-one. This transformation presumably proceeds through a conjugate addition or Diels-Alder cycloaddition of the 3-alkylindole with a 3-alkylindol-2-one intermediate.     

Total synthesis of (+/-)-cameroonanol

[reaction: see text]The structure and relative stereochemistry of the novel silphiperfolane-type sesquiterpene cameroonan-7alpha-ol (1) were confirmed by a total synthesis of (+/-)-1 from 3,3,5-trimethylbicyclo[3.3.0]oct-1(8)-en-2-one (6) by means of a Sakurai reaction with (Z)-crotylsilane, free radical hydrobromination, base-induced cyclization, and LiAlH4 reduction.     

Total synthesis of (+/-)-cytisine

[reaction:see text] The nicotine partial agonist cytisine was prepared in five steps featuring an "in situ" Stille or Suzuki biaryl pyridine coupling. Differentiation of the pyridyl rings was accomplished via selective benzylation and then reduction of a pyridinium ring. The penultimate diazabicyclo[3.3.1]nonane intermediate was obtained with high diastereoselectivity. A similar sequence has been employed for the synthesis of novel derivative 9-methoxycytisine.     

Total synthesis of (+/-)-symbioimine

The synthesis of (+/-)-symbioimine (1) has been completed in only 12 linear steps in 8% overall yield. The key step is the treatment of 13b with BF3.Et2O to generate N-carboalkoxydihydropyridinium cation 14b, which undergoes a novel stereospecific intramolecular Diels-Alder reaction to give adduct 16b in 42% yield. Cleavage of the N-Troc group of 16b afforded imine 24b stereospecifically. Cleavage of the TBDMS ethers and sulfation provided (+/-)-symbioimine (1). [reaction: see text].     

Total synthesis of (+/-)-galanthamine

[reaction: see text] A practical and efficient total synthesis of (+/-)-galanthamine was achieved from commercially available materials through a novel approach, in which the construction of its core structure and the special allylic alcohol group were based on a successive semipinacol rearrangement/desilyation/cyclization and Saegusa-Ito oxidation, respectively.     

Total synthesis of (+/-)-hasubanonine

[reaction: see text] Total synthesis of the alkaloid (+/-)-hasubanonine is described. A key feature of the route is generation of a phenanthrene intermediate via a Suzuki coupling-Wittig olefination-ring-closing metathesis sequence. Conversion of the phenanthrene into the target molecule required six steps including dearomatization by means of oxidative phenolic coupling, anionic oxy-Cope rearrangement, and a final acid-promoted cyclization. Production of an undesired rearranged product in the last step could be suppressed by moderating the acid strength.     

Total synthesis of (+/-)-biphyscion

[formula: see text] A regiospecific total synthesis of (+/-)-biphyscion (1) is described. A novel aspect of the plan was construction of the bianthraquinone ring system from a biphenyl intermediate through the use of a one-pot, double isobenzofuranone condensation.     

Total synthesis of (+/-)-psychotrimine

new process for the union of anilines with tryptamine derivatives has been developed, furnishing C-3 quaternized pyrroloindoline architectures. This chemoselective coupling of a tryptamine with 1.2 equiv of 2-iodoaniline proceeds efficiently on a gram-scale using only the simple reagents N-iodosuccinimide and triethylamine. Using this new reaction, the complex natural product psychotrimine has been fashioned with a rare level of efficiency and practicality. From a readily available bromotryptamine, only four steps (41-45% overall isolated yield) are necessary to procure gram quantities of the natural product. Functional group manipulations, protecting group chemistry, and unnecessary redox fluctuations have been minimized.     

Total synthesis of (+/-)-magnofargesin

[reaction: see text] A convenient method for the preparation of 2,5-dihydrofurans by using the chemistry of alkynyl(phenyl)iodonium salts is reported. Treatment of 3-alkoxy-1-alkynyl(phenyl)iodonium triflates with sodium benzenesulfinate generates an alkylidenecarbene, which undergoes [1,5]-C-H insertion to form 2-substituted 4-benzenesulfonyl-2,5-dihydrofurans in reasonable yield. These cyclic vinyl sulfones are functionalized in such a way as to make them useful starting materials for the preparation of lignans. The application of this methodology to the first total synthesis of (+/-)-magnofargesin is disclosed.     

Total synthesis of (+/-)-paeonilide

The total synthesis of paeonilide, a natural anti-PAF (platelet-activating factor) new skeleton monoterpenoid with an IC(50) value of 8 microg/mL, was achieved in 16 steps with 15% overall yield from commercially available 2-hydroxy-4-methylacetophenone. [reaction: see text]     

Total synthesis of (+/-)-isoschizogamine

[formula: see text] Isoschizogamine has been prepared for the first time. The synthesis requires eight steps from a readily available ketone starting material and features an aminal-forming cyclization that is based on a proposed biosynthetic transformation.     

Total synthesis of (+/-)-herbindole B and (+/-)-cis-trikentrin B

[reaction: see text] Herbindole B and cis-trikentrin B are naturally occurring indoles having the unusual and synthetically challenging pattern of carbon substitution at the 4-7 and 5-7 positions, respectively, with no substitution at the 1-3 positions. The total syntheses of these polyalkylated indoles have been achieved in 19 and 12 steps, respectively. The synthesis of herbindole B relies on two iterations of a quinine monoimine Diels-Alder reaction, while cis-trikentrin B uses a single cycloaddition of a suitable quinone monoimine. Indolization of the adducts provides suitably substituted benzopyrrole nuclei for elaboration to the natural products.     

Total synthesis of (+/-)-calcaridine A and (+/-)-epi-calcaridine A

The first total synthesis of the Leucetta alkaloid calcaridine A is described based on a biosynthetic postulate. Application of an oxidative rearrangement of a 4,5-disubstituted imidazole leads to the formation of both calcaridine A and epi-calcaridine A. An X-ray crystal structure determination on the latter has allowed the assignment of the relative configuration of the epimeric natural product and calcaridine A by extrapolation.