Synthesis of Enantiomerically Pure Substituted Cyclopentenes from (−)-Quinic Acid

The synthesis of a large variety of enantiomerically pure substituted reactive cyclopentenes 16, 23, 24 and 28 have been synthesized from the readily available (?)-quinic acid 1 . The straightforward strategy involves a high-yielding intramolecular aldolization-dehydration of acyclic 1,6-dialdehydes 13, 18, 19 and 27 obtained by oxidative cleavage of cyclohexanediols 5, 7, 11 and 12 , using either lead tetraacetate or triphenylbismuth carbonate. Neither sulfoxide formation nor racemization of the intermediate dialdehydes at the oxygenated chiral centre was observed. Transformation of the thioacetal 25 to the corresponding ketone 26 using phenylselenic anhydride is also described.     

First Atroposelective Total Synthesis of Enantiomerically Pure Ancistrocladidine and Ancistrotectorine

The first regio‐ and stereoselective total synthesis of the axially chiral 7,3′‐coupled naphthylisoquinoline alkaloids ancistrocladidine ( 1 ) and ancistrotectorine ( 2 ) has been described. Both possess a 7,3′‐coupled axis, which before now, was difficult to attain synthetically. Moreover, target 2 has a sensitive relative cis‐array of the two methyl groups at C1 and C3 in the tetrahydroisoquinoline part. The key step in the chosen strategy was the construction of the biaryl axis in accordance with the “lactone method”: the two molecular halves, which were activated in an “inverse‐halogenated” form, were prefixed by an ester bridge, followed by intramolecular coupling, and atroposelective cleavage of the lactone auxiliary bridge delivered the desired biaryl scaffold.     

A Facile Synthesis of Enantiomerically Pure (R)‐6‐Arylbinols

This work reported a convenient method for the preparation of enantiomerically pure 6‐aryl‐2,2′‐dihydroxy‐1,1′‐binaphthyl derivatives starting from the commercially available (R)‐2,2′‐hydroxy‐1,1′‐binaphthyl [(R)‐ 1 ] via bromination, hydrolysis and Suzuki cross coupling reaction. This novel synthetic method was characterized with high regioselectivity, simple operation, mild reaction conditions, and excellent yield (up to 73%). On the other hand, we synthesized the target unknown compounds, which were confirmed by IR, ¹H NMR, ¹³C NMR, MS and elementary analysis.     

First Total Synthesis of (−)‐Ligustiphenol

The first asymmetric total synthesis of (?)‐ligustiphenol is reported. The key step was conducted by exploiting a steric hindrance effect to control the formation of the adduct in a nucleophilic α‐Li‐phenolate addition reaction to the intermediate α‐oxo (?)‐menthyl ester. The synthesis is concise and feasible for the construction of analogous compounds and investigation of their biological activity.     

Total Synthesis of (−)-Mucocin

A highly convergent, modular strategy for the total synthesis of the annonaceous acetogenin (−)-mucocin is reported. The remarkable features are the endo-selective formation of the tetrahydropyran ring from an activated epoxide and the stability of the butenolide in the coupling with an organomagnesium compound.     

Enantiospecific Total Synthesis of (−)-D-Noviose

(−)-D -Noviose ((−)- 22 ), a rare sugar, was synthesized starting from the optically active building block (−)- 1 in seven steps. The first step of this route, the introduction of a methyl-ether group under Lewis-acidic conditions, left the acetoxy group untouched and thereby preserved the absolute configuration in the product 2 (Scheme 2). Next, the double bond of methyl ether 2 was cis-dihydroxylated leading selectively to 3 . After saponification of the acetoxy group of 3 the two vicinal cis OH groups of 17 were selectively protected as the cyclic carbonate 18 (Scheme 4). This kind of protection was essential to achieve the proper regioselectivity in the Baeyer-Villiger rearrangement of the cyclopentanone derivative 19 that was obtained after oxidation of the remaining OH group of 18 . Lactone 20 was the major product of this rearrangement. Final reduction to the corresponding lactol (cyclic hemiacetal) with diisobutylaluminium hydride (DIBAH) at low temperature was accompanied by reductive cleavage of the protecting cyclic carbonate moiety thereby leading directly to (−)-D -noviose ((−)- 22 ).     

Steroid Total Synthesis,Part II; (−)-17β-Hydroxy-des-A-androst-9-en-5-one

Based on the results obtained in the racemic series (part I), (—)-17β-hydroxy-des-A-androst-9-en-5-one has been synthesized, starting with (S)-(—)-5-heptanolide. The key step, viz. the condensation of (S)-(—)-7-hydroxy-1-nonen-3-one (or its amine adduct) with 2-methyl-cyclopentane-1, 3-dione involves an asymmetric induction. Model experiments with (R)-(+)-5-decanolide leading to the enantiomeric homolog of the BCD-tricyclic compound are also described.     

The First Enantiomerically Pure Triangulane (M)-Trispiro

A remarkably high specific rotation, even at 589 nm, is shown by (M)-1, the first enantiomerically pure unbranched [4]triangulane, although it has no chromophore that would lead to any significant absorption above 200 nm. This outstanding rotatory power is in line with a helical arrangement of its sigma bonds, as confirmed by high-level computations. Thus, it is appropriate to call (M)-1 a "sigma-[4]helicene", the first sigma-bond analogue of the aromatic [n]helicenes.     

Total Synthesis of (−)-(2R)-Dihydromyricoidine

An asymmetric synthesis of the spermidine alkaloid (?)-(2R)-dihydromyricoidine ( 5 ) was performed by employing two ring-enlargement reactions. The chiral center was introduced by a diastereoselective Michael addition of perhydropyridazine ( 7 ) to the α,β-unsaturated ester 6 . The (Z)-C?C bond was obtained by a selective Wittig reaction. The synthetic compound 5 was found to have a negative value for the specific rotation. This is in contrast to that of the natural product reported in the literature. Therefore, as an outcome of this synthesis, the absolute configuration of the natural alkaloid should be inverted to be as shown in structure V .     

Total Synthesis of (−)‐Daphenylline

Total synthesis of (?)‐daphenylline, a hexacyclic Daphniphyllum alkaloid, was achieved. Construction of the tricyclic DEF ring system was initiated by asymmetric Negishi coupling followed by an intramolecular Friedel–Crafts reaction. Installation of a side chain onto the tricyclic core was carried out through Sonogashira coupling, stereocontrolled Claisen rearrangement by taking advantage of the characteristic conformation of the tricyclic DEF core, and the stereoselective alkylation of a lactone. After the introduction of a glycine unit, the ABC ring system was stereoselectively constructed through intramolecular cycloaddition of the cyclic azomethine ylide.     

Total Synthesis of (−)‐Isoschizogamine

The total synthesis of (?)‐isoschizogamine was accomplished, featuring the construction of the quaternary carbon center by the modified Johnson–Claisen rearrangement in basic media and the facile assembly of the key tetracyclic quinolone intermediate through a cascade cyclization. The characteristic cyclic aminal was constructed by late‐stage C?H functionalization at the position adjacent to the lactam nitrogen using a combination of CrO₃ and nBu₄NIO₄ and subsequent Bi(OTf)₃‐mediated cyclization.