The total synthesis of (−)-connatusin A, a hirsutane-type sesquiterpene isolated from the fungus Lentinus connatus BCC8996

The title sesquiterpenoid natural product 1 has been prepared for the first time using the enantiomerically pure cis-1,2-dihydrocatechol 3 as starting material. Key steps associated with the synthesis include a Diels-Alder cycloaddition reaction of the acetonide 5 with cyclopentenone (4) and an oxa-di-π-methane rearrangement of bicylco[2.2.2]octenone 6 derived from the initial adduct. The product of this sequence, the cyclopropannulated triquinane 7, was elaborated, over a further eight steps including those involving Upjohn dihydroxylation and Swern oxidation protocols, to the target 1. A single-crystal X-ray analysis served to confirm the structure of this synthetically derived material.     

Formal total synthesis of aspergillides A and B

The formal total synthesis of the cytotoxic 14-membered macrolides, aspergillides A and B is described. A combination of a chiron approach and an asymmetric synthesis is adopted for the synthesis of the target macrolides. The required 2,6-syn and 2,6-anti tetrahydropyrans were constructed via a tandem Sharpless asymmetric epoxidation and 6-exo cyclization on δ-hydroxy allylic alcohols, as the key steps. The requisite chiral synthon was prepared from l-ascorbic acid.     

The first stereoselective synthesis of dendrodolide A

The first stereoselective total synthesis of natural product, dendrodolide A (1) is described from readily available (R)-propylene oxide and 3-buten-1-ol as starting materials. The synthesis was achieved in 10 steps with an overall yield of 19.1%. The key steps involved in the synthesis are Jacobsen hydrolytic kinetic resolution, epoxide ring opening with 2-allyl-1, 3-dithiane, Yamaguchi esterification, and ring-closing metathesis (RCM).     

Improved total synthesis of (±)-Tetragocarbone A

Stereoselective total synthesis of (±)-tetragocarbone A isolated from the propolis of an Australian stingless bee, Tetragonula carbonaria, has been developed by focusing on the latent symmetry of 1. The requisite 1R*, 3R*, 6S* stereogenic centers were selectively installed by hydroxy group directing reactions including the late stage desymmetrization of the 1,3-diketone. The target natural product was successfully prepared in 12 steps from phloroglucinol on 300 mg.     

A versatile approach to cis-5-substituted 4-hydroxy-2-pyrrolidinones: asymmetric synthesis of angiogenesis inhibitor streptopyrrolidine

A concise, flexible, and highly diastereoselective approach to cis-5-alkyl-4-hydroxy-2-pyrrolidinones 1 is described. The key step is an ammonium acetate-assisted catalytic hydrogenation of the enamides 9, derived in two steps from malimides 6a,b as we have described previously. The method was applied to the asymmetric synthesis of streptopyrrolidine 5, a natural product, which exhibited significant anti-angiogenesis activity.     

A four step synthesis of violaceic acid

The total synthesis of the biaryl ether natural product violaceic acid (1) in four steps is described. The steps included a S_NAr reaction between phenol 7 and flouroarene 12 to afford the biaryl ether 13, selective reduction of a nitro group to an amine in the presence of an aldehyde, a Cu mediated Sandmeyer reaction and final hydrolysis to afford the target compound 1. The amine 14 was also converted into the known iodide 18 which gave impure 1 on Pd mediated hydroxide cross coupling.     

Concise synthesis of a pentasaccharide repeating unit corresponding to the O-antigen of Escherichia coli O102

An efficient synthetic strategy has been developed for the synthesis of a pentasaccharide repeating unit of the O-antigen of Escherichia coli O102 strain. The target pentasaccharide 1 has been synthesized using a [2+3] block glycosylation strategy. All glycosylation steps are highly stereoselective and high yielding. Concept of armed-disarmed and orthogonal glycosylation strategies has been applied during the synthesis. The target compound has been synthesized using the minimum number of steps.     

A simple and efficient enantioselective route to 2,6-disubstituted piperidines: synthesis of (2R,6S)-isosolenopsin A and (2S,6R)-isosolenopsin

The enantioselective synthesis of 2,6-cis-disubstituted piperidine alkaloids, (2R,6S)-isosolenopsin A 2 and (2S,6R)-isosolenopsin 5 from fire ant venom is described. Starting from the dodecanal and decanal, the synthesis presents two key steps. The first step involves Keck allylation to afford the chiral homoallylalcohol with the required stereochemistry and the second key step consists of Grubbs olefin cross metathesis. The synthesis was achieved in five steps with 44% overall yield.     

Chemoenzymatic synthesis of heparan sulfate tetrasaccharide from a N-acetyl-α-d-glucosamine-O-methylglycoside acceptor

Heparan sulfate tetrasaccharide 2 was efficiently prepared in seven steps through chemoenzymatic synthesis. A monosaccharide 5, N-acetyl-α-d-glucosamine- O-methylglycoside (GlcNAc-OMe), was successfully used as an acceptor in a heparosan synthase (pmHS2)-catalyzed glycosylation reaction. This avoided the multi-step synthesis of a more complex disaccharide acceptor 3, greatly simplifying the route to tetrasaccharide target 2. This approach provides a critical tetrasaccharide intermediate for subsequent chemoenzymatic transformation to fondaparinux and its analogues.     

Stereoselective total synthesis of ieodomycin C

A concise stereoselective synthesis of the marine natural product ieodomycin C (3) has been achieved from commercially available pyridinium-1-sulfonate (8) in eight linear steps and 14% overall yield. The key synthetic steps included a B-alkyl Suzuki–Miyaura cross-coupling reaction and an Evans–Nagao acetate aldol reaction. The same synthetic sequence was used for preparing the enantiomer of ieodomycin C (3). Our efforts confirmed the structure of the antibacterial natural product 3.     

An asymmetric synthesis of sulfobacin A

A facile synthesis of sulfobacin A has been developed starting from (R)-cyclohexylideneglyceraldehyde (11). The key steps in the synthesis are the highly diastereocontrolled allylation of 11 and syn-selective reduction of a ketone derived from 11. The other attractive features are the operational simplicity and the use of inexpensive compounds/reagents.     

A short and efficient asymmetric synthesis of komaroviquinone

An asymmetric total synthesis of komaroviquinone (1), which is a natural product isolated from Dracocephalum komarovi and shows novel potent trypanocidal activity, was achieved in five steps from the known starting materials. The synthetic route is shorter and more efficient than the reported methods and also useful for the scale-up synthesis.     

New total synthesis of (+)-ambrein

The convergent synthesis of (+)-ambrein 1 was achieved based on a modified Julia coupling reaction between aldehyde 14 corresponding to the left-half A and sulfone 25a or 25b corresponding to the right-half B. Aldehyde 14 was synthesized in 14% overall yield (nine steps) from the enzymatic resolution product, epoxy alcohol (8aS)-2. Sulfone 25a or 25b was synthesized in 11 steps (25a: 41% overall yield, 25b: 56% overall yield) from the enzymatic resolution product, (1S,6S)-2,2-dimethyl-6-hydroxyhexane-1-carboxylate 4.     

Total synthesis of diaportheone A

Diaportheone A (1), a chromone natural product was previously isolated from the endophytic fungi Diaporthe sp. P 133. Its structure was established by spectroscopic methods, however, its absolute configuration remained undefined. This study dealt on the total synthesis of diaportheone A (1) utilizing the cyclization and in situ thermal syn-elimination of a β-ketosulfoxide. The C-1R absolute configuration of the natural product was established by X-ray crystallography of the synthetic diaportheone A (1) (>99%?ee) and comparison with the optical rotation.     

Enantioselective allyltitanations: synthesis of the proposed structures for passifloricin A

The stereoselective total synthesis of the proposed structures P1 and P2 for passifloricin A was achieved in 12 steps from n-hexadecanal by using enantioselective allyltitanations and a ring closing metathesis reaction as the key steps. Both P1 and P2 are different from passifloricin A.     

Synthesis ofa trimeric lignin model compound composed ofol-O-4 and β-O-4 linkages under microwave irradiation

A trimeric lignin model compound composed of α-O-4 and β-O-4 linkages was prepared by the microwave-assisted synthesis, which consisted of three steps： （a） the synthesis of 3-methoxy-4- benzyloxyacetophenone （2） from acetovanillone （1）, （b） the bromination of compound 2 to produce 3- methoxy-4-benzyloxy-α-bromoacetophenone （3）, and （c） followed by a nucleophilic substitution of compound （3） to obtain 3-methoxy-4-benzyloxy-α-（3-methoxy-4-（1-propenyl）phenol）-acetophenone （4）. The target product was characterized by MS, 1H NMR and 13C NMR spectroscopy. It was found that the trimeric compound synthesized can be used as a preferable lignin model compound because it contains guaiacyl structural unit （3-methoxy-4-hydroxy phenyl propane） linked by α-O-4 and β-O-4 linkages. In addition, under the conditions of microwave irradiation, the reaction time of each step is significantly reduced, and the selectivity of target product is greatly improved. The yields of each step and the overall sequence are 95.31%. 87.3%. 90.6% and 75.4% （95.31%× 87.3% × 90.6%）. respectively.     

SN2 reaction of 2-substituted 3-piperidinol mesylate with retention of configuration: application to the asymmetric synthesis of (2R,3S)-CP-99,994

Starting from protected (S)-3-hydroxyglutarimide 2a, the asymmetric synthesis of (2R,3S)-CP-99,994 8 was achieved. The crucial steps were a neighboring group participation leading to pyrrolidino-aziridinium intermediate 25 and the subsequent regioselective ring-opening reaction. In the case where neighboring group participation was not involved, only the eliminated product 15 was obtained.     

Polycyclic hydroxyquinones—VIII: Preparation of acetylhydroxynaphthazarins by photo-fries rearrangement. A convenient synthesis of spinochrome A

Several synthetic routes to mono- and dihydroxynaphthazarins bearing an acetyl side-chain have been explored. Methoxynaphthazarin1 has always been the starting material. Acylation is brought aboutvia a photo-Fries rearrangement of various adequately substituted acetoxynaphthalenes prepared in several steps from1. Further steps including oxidative demethylation, hydrolysis and ether cleavage reactions, led to the desired mono- and dihydroxysubstituted acetylnaphthazarins. A new synthesis of Spinochrome A24, a natural occurring pigment representative of this kind of naphthazarin derivatives, is described.     

A stereorational total synthesis of (−)-ptilocaulin

A stereorational total synthesis of the structurally (?)-enantiomer of the unique guanidine containing natural product ptilocaulin is described. This efficient synthesis (14 steps, 7.4% overall yield) utilizes an intramolecular 1,3-dipolar cycloaddition as a key step and establishes that the natural product is the most stable of a number of possible isomers. This work also establishes the absolute stereochemistry of ptilocaulin to be that shown in formula 3.     

Convergent synthesis of a common pentasaccharide-repeating unit corresponding to the O-specific polysaccharide of Escherichia coli O4:K3, O4:K6, and O4:K12

A convergent chemical synthesis of a pentasaccharide found in the O-specific polysaccharide of Escherichia coli O4:K3, O4:K6, and O4:K12 has been achieved in excellent yield. A [3+2] block synthetic strategy has been adopted to couple a disaccharide donor 11 with a trisaccharide acceptor 10 for the construction of the pentasaccharide derivative 12 which on deprotection furnished target pentasaccharide 1 as its 4-methoxyphenyl glycoside. Disaccharide thioglycoside donor 11 and trisaccharide acceptor 10 were prepared from suitably protected monosaccharide intermediates. Yields were excellent in all steps.