(±)-19-去甲基-4(18),8,11,13-四烯-松香烷-7-酮的全合成

以间异丙基溴苯1为起始原料,通过进攻环氧乙烷及溴代两步制得溴化物3.溴化物3与Hagemann′s酯发生偶联反应,水解后生成偶联产物5.再以路易斯酸BF3·Et2O催化化合物5进行分子内环化为关键步骤得到反式稠合中间体6,最后通过与三苯基膦碘甲烷季盐发生Wittig反应及氧化,合成了(±)-19-去甲基-4(18),8,11,13-四烯-松香烷-7-酮[19-nor-abieta-4(18),8,11,13-tetraen-7-one](8).     

Total syntheses via cyclopropanols

Cyclopropanols are readily available via the Kulinkovich cyclopropanation, the Simmons-Smith reaction, and other synthetic methods. Due to their intrinsic ring stains, cyclopropanols and their derivatives are highly reactive and can be converted to different structural scaffolds which are frequently found in many natural products. In this review, we highlight the applications of various cyclopropanol ring opening/expansion/fragmentation reactions in the total syntheses of natural products.     

Total syntheses of the proposed structures of cuevaene A

Two proposed structures of cuevaene A were synthesized and the NMR spectra of both structures are proved to be inconsistent with those of the natural product. The structure of cuevaene A is still unclear and needs to be revised.     

Total synthesis of (+)-trans- dihydronarciclasine from (+)-7-azabicyclo[2.2.1]heptanone

A concise asymmetric total synthesis of Amaryllidaceae alkaloid (+)-trans-dihydronarciclasine is accomplished starting from optically pure 7-azabicyclo[2.2.1]heptanone scaffold in 13 linear steps. Key features of the strategy include substrate-directed stereoselective installation of the trans B-C ring junction and regioselective Wacker-type internal olefin oxidation to provide a rapid access to all hydroxyl functionalities over the key cyclohexane ring in a stereocontrolled manner.     

Total syntheses of bupleurynol and its analog

An efficient route to the natural products bupleurynol and its analog (RB-2), isolated from Bupleuri Radix, was established based on versatile intermediate (15). In this synthetic route, Sonogashira and Cadiot-Chodkiewicz coupling as well as Julia-Kocienski olefination are utilized as key steps. The highly efficient synthetic route provides opportunities to explore the biological behavior of bupleurynol and RB-2.     

Diastereoselective approach to trans-5-hydroxy-6-substitutedethanone-2-piperidinones: Scalable syntheses of (+)-febrifugine and (+)-halofuginone

An efficient diastereoselective approach to access trans-5-hydroxy-6-substitutedethanone-2-piperidinones skeleton has been developed through sequential addition-deprotection-cyclization process involving aldimine 6 with substituted acetones. The diastereoselectivity of substitution at C-6 position of 2-piperidinone was controlled by α-siloxyl group and chiral sulfinamide moiety. In addition, the utility of this effective approach is demonstrated by the scalable syntheses of (+)-febrifugine (2) and (+)-halofuginone (4).     

Total syntheses of cyclitol based natural products from myo-inositol: brahol and pinpollitol

Inositol and their derivatives are important class of biologically active natural products. Among the nine theoretically possible inositols, six are known to occur in nature. Interestingly one or more methyl ethers of these inositols have been isolated from plants and these methyl inositols are presumed to have important functions in plant biology. Brahol and pinpollitol are two naturally occurring methylated inositols reported to have allo-inositol and chiro-inositol configurations, respectively. Adopting our sulfonate inversion strategies for synthesizing protected chiro- and allo-inositols from cheaply available myo-inositol in combination with new methods we have achieved the total syntheses of these methylated inositols. The proposed structure of brahol has been synthesized in six steps from myo-inositol. We have not only disproved the proposed structure of brahol but also established its correct structure. Also, we have efficiently synthesized pinpollitol and its positional isomer from myo-inositol. These works involve several selective protection-deprotection strategies of inositol hydroxyl groups.     

Total synthesis of (+)-bongkrekic acid

Total synthesis of bongkrekic acid, an important apoptosis inhibitor, has been accomplished. The strategy includes inexpensive starting materials, asymmetric alkylation, anionic allyl coupling and oxidative manipulations. This process would provide a sufficient amount of bongkrekic acid and its analogues.     

Total syntheses of (+)-australine and (-)-7-epialexine

Three approaches were examined for the synthesis of 3-(hydroxymethyl)pyrrolizidines, a class of compounds that includes the polyhydroxylated pyrrolizidine alkaloids alexine (1), australine (2), and various stereoisomers of thereof. In the first approach, the intramolecular cycloaddition of an azide onto an electron-rich 1, 3-diene bearing a terminal alkoxymethyl substituent (i.e., 21) afforded the dehydropyrrolizidines 22a and 22b, with 22a predominating. A rationale for this stereoselectivity was proposed. Transformation of the major diastereomer 22a into a natural 3-(hydroxymethyl)pyrrolizidine was not possible due to difficulties encountered in transforming the phenyl vinyl sulfide functionality into other useful functional groups. A second approach was examined, wherein the intramolecular cycloaddition of an azide with an optically pure S-t-Bu-substituted diene (i.e., 30) was found to produce the pyrrolizidine 31. In this case, the alkoxymethyl substituent was incorporated into the tether between the azide and the diene, rather than on the diene itself. A key transformation in the synthesis of the diene 30 was the use of the allylic borane R(2)BCH(2)CH=C(TMS)(StBu) for the stereoselective conversion of the D-arabinose-derived azido aldehyde 28 to the E-isomer of 30. The cyclization of 30 to 31 also produced the bicyclic triazene 32, the result of 1,3-dipolar cycloaddition of the azide onto the distal double bond of the diene. Again, difficulties in transformation of the vinyl sulfide functionality of 31 into useful oxygen functionality limited this approach to naturally occurring 3-(hydroxymethyl)pyrrolizidines. A third approach to these compounds was successful. The transformation of L-xylose into the azido epoxy tosylate 46 was accomplished using two Wittig reactions and an epoxidation, in addition to other standard functional group manipulations. Reductive double-cyclization of 46 afforded the pyrrolizidines 47a and 47b, which were debenzylated to afford (+)-australine 2 and (-)-7-epialexine 4, respectively. In the preliminary report of this work, erroneous spectroscopic data in the original literature on the structural assignment of australine led to the conclusion that the synthetic material obtained herein was actually (+)-7-epiaustraline. Recently corrected spectroscopic data have appeared which verify that (+)-australine 2 was indeed synthesized for the first time.     

Total syntheses of (±)-cis- and (±)-trans-neocnidilides

Total syntheses of two antimicrobial natural products (±)-cis-neocnidilide and (±)-trans-neocnidilide starting from a readily preparable cyclohexa[b]-fused 5-oxabicyclo[2.1.1]hexane derivative are presented. The diastereomeric tetrahydrofuran tricarboxylate epimers obtained from a BF₃·OEt₂ promoted Grob-type fragmentation of the oxa-bicycle derivative were converted into title natural products by employing pyridinium dichromate/acetic anhydride mediated bis-oxidative cleavage reaction.     

Enantiodivergent syntheses of (−)- and (+)-dysibetaine CPa and N-desmethyl analog

The first total syntheses of (−)-dysibetaine CPa and the antipode have been achieved using enantioselective solvolysis of meso-cyclic anhydride mediated by quinine derivative as an organocatalyst. The synthesis features a demonstration of an enantiodivergent organic synthesis of both enantiomers of dysibetaine CPa whereby the absolute configurations of natural product were elucidated as (3R,4R). Application of the present methodology to an enantiomerically pure novel GABA analog is also reported.     

First total synthesis and determination of the absolute configuration of 1-N-methyl-3-methylamino-[N-butanoicacid-3-(9-methyl-8-propen-7-one)-amide]-benzo[f][1,7]naphthyridine-2-one, a novel benzonaphthyridine alkaloid

The first total synthesis of benzonaphthyridine alkaloid (1), a unique diazaphenathrene alkaloid isolated from mangrove-derived Streptomyces albogriseolus, was accomplished. The core structure was unequivocally constructed via several key transformations, such as Knoevenagel condensation, Curtius rearrangement, and cyclic carbamate formation-reduction sequence. The chiral unsaturated ketone acid moiety was synthesized from N-tert-butoxycarbonyl-l-glutamic acid gamma-tert-butyl ester (15). The absolute configuration was determined.     

Total syntheses of (+)-7-epi-goniofufurone, (+)-goniopypyrone and (+)-goniofufurone from a common precursor

Total syntheses of (+)-7-epi-goniofufurone, (+)-goniopypyrone and (+)-goniofufurone have been achieved from an advanced common precursor formed from D-(+)-mannitol by changing the carbinol protection profile.     

Total syntheses of (+)-tedanolide and (+)-13-deoxytedanolide

Convergent total syntheses of the potent cytotoxins (+)-tedanolide (1) and (+)-13-deoxytedanolide (2) are described. The carbon framework of these compounds was assembled via a stereoselective aldol reaction that unifies the C(1)-C(12) ketone fragment 5 with a C(13)-C(23) aldehyde fragment 6 (for 13-deoxytedanolide) or 52 (for tedanolide). Multiple obstacles were encountered en route to (+)-1 and (+)-2 that required very careful selection and orchestration of the stereochemistry and functionality of key intermediates. Chief among these issues was the remarkable stability and lack of reactivity of hemiketals 33b and 34 that prevented the tedanolide synthesis from being completed from aldol 4. Key to the successful completion of the tedanolide synthesis was the observation that the 13-deoxy hemiketal 36 could be oxidized to C(11,15)-diketone 38 en route to 13-deoxytedanolide. This led to the decision to pursue the tedanolide synthesis via C(15)-(S)-epimers, since this stereochemical change would destabilize the hemiketal that plagued the attempted synthesis of tedanolide via C(15)-(R) intermediates. However, use of C(15)-(S)-configured intermediates required that the side-chain epoxide be introduced very late in the synthesis, owing to the ease with which the C(15)-(S)-OH cyclized onto the epoxide of intermediate 50.     

Total syntheses of Lycopodium alkaloids (+)-fawcettimine, (+)-fawcettidine, and (-)-8-deoxyserratinine

A shared story: Three fawcettimine- and serratinine-type Lycopodium alkaloids are prepared from a common tetracyclic spirodiketone intermediate in concise total syntheses. The intermediate was constructed by a remarkable biosynthesis-inspired transannular N-C bond formation to the spiro-configured carbon center and a hydroxy-directed pinacol coupling promoted by SmI(2).     

First total syntheses of (+)-7-deoxynogarol and (+)-7-con-o-methylnogarol

The first total syntheses of (+)-7-deoxynogarol (2) and (+)-7-con-O-methylnogarol (3), the notable members of nogalamycin congeners, were achieved employing the Diels-Alder reaction of the highly functionalized dienes (11 and 20) with the (+)-naphthoquinone (6), the CDEF-ring system of nogalamycin congeners, as a key synthetic step.     

Asymmetric total syntheses of heliannuol E and epi-heliannuol E

Asymmetric total syntheses of heliannuol E and epi-heliannuol E were achieved in 10 and 13 steps, respectively, from the commercially available starting materials. The syntheses feature an intramolecular attacking on the sulfate to form the dihydropyran ring of heliannuol E and an acyl transfer-secondary carbocation capture sequence to construct the dihydropyran ring of epi-heliannuol E.     

First enantioselective synthesis of methyl (+)-7-methoxyanodendroate, an antitubercular dihydrobenzofuran

An enantioselective synthesis of methyl (+)-7-methoxyanodendroate was achieved utilising a Claisen rearrangement, a Grubbs cross-metathesis, and a Shi epoxidation-cyclisation sequence, confirming the absolute configuration assigned to the natural product.     

An overview of the total synthesis of africane-type sesquiterpenoids

Africane-type sesquiterpenoids consist of a bicyclo[5.3.0]decane structure and have been isolated from various natural environments. Their characteristic CC bond motifs, including a seven-membered ring core, fascinate many synthetic organic chemists. Thirteen total syntheses have been reported over the past four decades. The purpose of this digest is to provide an overview of these total syntheses of africane-type sesquiterpenoids, with an emphasis on methods for constructing the seven-membered ring structure.