Tricyclic diterpenoids synthesis

Homoallylic alcohols are also suitable for controlling the introduction of an alkyl chain, as shown by the synthesis of the diterpenoid atractyligenin61, The starting tricyclic alcohol is converted to the selenocarbonate, a suitable radical precursor. Treatment with tributyltin hydride initiates the stereoselective cyclization which affords the bridged lactone system, an intermediate in the diterpenoid synthesis. Due to the low cyclization rate, tributyltin hydride is added slowly to suppress the formation of noncyclized reduction products. 

PhiUips et al. designed the tandem RRM reaction of bicyclic compounds having two reactive sites in side chains to synthesize a tricyclic diterpenoid cyanthiwigin U 137, which is isolated from both fungal and marine sources (Scheme 24.35). The two-directional tandem ROM-RCM sequence of bicyclo[2.2.2]-octane 135 was catalyzed by [Ru]-II (20mol%) under the ethylene atmosphere, and transformations of tricyclic compound 136 completed a synthesis of this natural product in 17% overall yield in 12 steps. 

The same authors also used this approach for an enantioselective synthesis of the natural product (-i-)-royleanone (4-54), a member of the abietane diterpenoid family [17]. The enantiopure sulfoxide 4-50 was oxidized using DDQ to give crude 1,4-ben-zoquinone 4-51, which by reaction with the diene 4-52 in CH2C12 under high pressure led to the tricyclic compound 4-53 with 97 % ee and 60% yield based on 4-50 (Scheme 4.11). Hydrogenation of the unconjugated double bond in 4-53 afforded 35% of the desired compound 4-54 after crystallization to separate it from the unwanted cis-isomer. 

Since the discovery of the high anticancer activity of taxol, much attention has been drawn to its asymmetric synthesis. The total synthesis stood for more than 20 years as a challenge for organic chemists. The compound taxoids are diterpenoids isolated from Taxus species and have a highly oxidized tricyclic carbon framework consisting of a central eight-membered and two peripheral six-membered rings (see Fig. 7-2).21... 

We have found that intramolecular Friedel-Crafts alkylations of conjugated dienones permit the efficient preparation of functionalized hydrophenanthrenes (Equation 5.1).21 Since this represents a new strategy for the synthesis of 6,6,6-fused tricycles, we sought to demonstrate its utility through the total syntheses of miltirone (56) and two closely related diterpenoids sageone (57), which possesses significant antiviral activity,22 and arucadiol (58), 23... 

Meyer and co-workers reported (184) a simple synthesis of a tricyclic intermediate containing the ABE ring system. The sequence for the synthesis of 398 is outlined in Scheme 3. Compound 398 is of interest as an intermediate for synthesis of C20-diterpenoid alkaloids containing a substituent at the C-7 position, e.g., ajaconine, atidine, and spiradine. 

During a total synthesis of the diterpenoid enmein, the tricyclic alcohols (47) and (48) were converted into a range of c-ring ketones (Scheme 5). The degree of reduction and the ease with which it occurs, relative to (23), make it apparent that intramolecular protonation is involved here also. ... 

The asymmetric total synthesis of the putative structure of the cytotoxic diterpenoid (-)-sclerophytin A was realized via a Tebbe-Claisen rearrangement of a tricyclic lactone precursor in the laboratory of L.A. Paquette/ The tricyclic lactone was subjected to the Tebbe methylenation protocol to provide the allyl vinyl ether that was then heated to 130-140 °C in p-cymene to undergo the Claisen rearrangement in good yield. 

The total synthesis of the marine-derived diterpenoid sarcodictyin A was accomplished in the laboratory of K.C. Nicolaou. The most challenging part of the synthesis was the construction of the tricyclic core, which contains a 10-membered ring. This macrocycle was obtained by the intramolecular 1,2-addition of an acetylide anion to an a, 3-unsaturated aldehyde. This unsaturated aldehyde moiety was installed by utilizing the Knoevenagel condensation catalyzed by (3-alanine. The Knoevenagel product was exclusively the ( )-cyanoester. 

A new synthesis of sempervirol has utilized the condensation " of j8-cyclocitral with 4-isopropyl-3-methoxybenzyl chloride to afford (108). Cyclization of the corresponding ketone gave the tricyclic system (109) which was converted into sempervirol. A novel rearrangement of the angularly fused cyclobutanone (110) to (111) forms the basis of a synthesis of potential intermediates for conversion into the diterpenoid alkaloids. 

Cu-Bisoxazoline-catalyzed asymmetric cyclopropanation of methyl 2-furoate with ethyl diazoacetate was a key step in the synthesis of the cw-fused 5-oxofuro[23-fc]furan core of spongiane diterpenoids <05OL5353>. An interesting example of rtiodium-catalyzed intramolecular addition of a diazoketone to furan affording a strained cyclobutenone, is illustrated below. Iodine-induced isomerization of the product provided the fused tricyclic dihydrofuran compound <05HCA33Q>. 

The cyathane diterpenoids have a characteristic 5-6-7 membered tricyclic skeleton. Piers et al. reported the synthesis of one of the cyathane diterpenoids, ( )-sarcodonin G (198) [58]. In this synthesis, a mixture of 196 and 197 (30 1) obtained from selenide 195 by oxidation, cleanly isomerized to give thermodynamically favoured 197 in the reaction with DBN in refluxing benzene (Scheme 7.45). 

A number of major synthetic achievements in the diterpenoid area have been reported during the year. One of these has been the completion of the total synthesis of the insecticidal diterpenoid ryanodol (95) from the two units (93) and (94). The more highly oxidized diterpenoid phenols have attracted attention. Syntheses of the tricyclic phenol cryptojaponol, taxodione, and coleon and approaches to coleon and coleon have been reported. 

Similarly, the bicyclo[2.2.2]octene double bond in 28 was readily opened in a domino ROM/double RCM process, leading to tricyclic bisenone 29 with catalyst 2 under ethylene atmosphere in good overall yield from dialdehyde 27 (Scheme 2.11) [7]. Compound 29 was successfully utihzed as the key intermediate in a total synthesis of the bioactive diterpenoid (-l-)-cyanthiwigin U. 

The first total synthesis of this natural product was achieved by Chiu and Lam [139]. Key step of the synthesis is a rhodium-catalyzed domino cychza-tion/cycloaddition reaction to form the tricyclic core of the diterpenoid from hnear a-diazoketone 337. Concerning the mechanism of the reaction, it is hkely that the rhodium catalyst, when reacted with 337 at 0 °C, formed a carbenoid species which immediately cyclized to 341 (Scheme 14.53). This 1,3-dipole then underwent an intramolecular cycloaddition with the aUcene to give a mixture of two cycloadducts in 81% yield with 339 as the major product (dr= 1 3.1 338 339). The minor diastereomer 338 was probably formed via a less stable boat conformation of the tether in contrast to the chair conformation shown in 341, leading to the desired product Decreasing the temperature from 0 to —15 °C did not increase the dr but lowered the yield. It is also remarkable that the reaction afforded no more than 0.5 mol% of the rhodium(II)octanoate dimer ([Rh2(Oct)4]). Further transformation of 339 finally furnished (—)-indicol (340) in an overall yield of 10% over 21 steps. 

Synthesis of Taiwaniaquinol Diterpenoids Taiwaniaquinol diterpenoids present a 6,5,6-ABC tricyclic skeleton relatively uncommon in natural products. Their intriguing structures and their biologically significant activities have attracted the attention of organic chemists. She s... 

The Peterson olefination is known for its better performance compared to the corresponding Wittig process for hindered substrates. This is demonstrated in the first asymmetric synthesis of (+)-maritimol, a member of the stemodane diterpenoids (eq 66). Thus, the key step, a Thorpe-Ziegler annulation, requires a 1,5-dinitrile motif. This is achieved by the generation of an a-silyl boronate, obtained by BuLi deprotonation of trimethylsilylace-tonitrile and subsequent transmetalation with triisopropyl borate, which is then condensed with the tricyclic aldehyde. ... 

While neovibsanins consist of tricyclic unusual diterpenoid stmcture, it is important to clarify the structural factors of the neovibsanin skeleton that are essential for exerting its biological activity for further studies on drug development. In 2009, Williams et al. reported that the stereochemistry at the 4 and 5 positions on the neovibsanin skeleton has very little effect on neurotrophic activity via the synthesis of unnatural 4,5-bi-epi-neovibsanins [53]. In the same year, we completed the first total synthesis of ( )-neovibsanin B, which shows identical activity as that of natural (+)-63 [46]. 

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