Dolastane synthesis

In the course of dolastane synthesis (the dolastanes are a group of marine diterpenes) interesting rearrangements catalyzed by Lewis acids were found. Treatment of the trienone 293 with excess (1.5 eq) ethylaluminum dichloride at low temperatures (—5°C, 48 h) gave the tetracyclic enone 295 in 53% yield while the tricyclic dienone 296 (50%) was formed at room temperature (equation 102)156. It was assumed that both products can be derived from the common zwitterion 294 which undergoes intramolecular alkylation at low temperatures (path a) whereas an alkyl shift takes place at elevated temperatures (path b), followed by a 1,2-hydride shift (equation 102). 

Hiersemann M, Helmboldt H (2005) Recent Progress in the Total Synthesis of Dolabellane and Dolastane Diterpenes. 243 73-136... 

Recent Progress in the Total Synthesis of Dolabellane and Dolastane Diterpenes... 

Abstract The isolation, structure and total synthesis of members of four classes of diterpenes has been summarized. Dolabellanes, neodolabellanes, dolastanes and neodolas-tanes are structurally related bi- or tricyclic diterpenes. Dolabellanes belong to a continuously growing class of diterpenes being isolated from marine and terrestrial sources. The published work on isolation and synthesis since 1998 has been summarized. Neodolabellanes represent a scarce class of diterpenes that have been isolated exclusively... 

Total Synthesis Natural Product Dolabellane Dolastane ... 

The vast majority of total syntheses of dolastanes and dolabellanes rely on more or less linear strategies. The total synthesis of (+)-4,5-deoxyneodola-... 

The first total synthesis of a racemic dolastane (rac-llO) was apparently published by Pattenden as a short communication 1986 followed in 1988 by a full paper [77, 78]. Pattenden s strategy is based on an intramolecular [2+2]-photocycloaddition/cyclobutane fragmentation to transform the diene 133 into the hydroazulene 136 (Scheme 20). In between the cycloaddition... 

The total synthesis of the natural ( )-l(15),7,9-dolastatrien-14-ol (( )-122) was reported in 1986 by Piers and Friesen (Scheme 21) [80]. The hydroazulene 143 served as key intermediate and the C-ring was annulated by an intramolecular Grignard reaction of the vinyl magnesium ketone 144 to provide the desired dolastane (+)-122 in moderate yield as a single... 

Starting with the intermediate ( )-145 of the aforementioned total synthesis of ( )-122, Piers realized the synthetic access to the racemic dolastane ( )-124 (Scheme 22) [82, 83]. An intramolecular Stille coupling served as key step, this time for the annulation of the C-ring. 

The synthesis of the non-natural ( )-7,14-epz-l(15),8-dolastadien-7,14-ol (rac-7yl4-epi-l09) was published by Paquette in 1986 and is highlighted by a photochemical rearrangement of the 6,6,6-tricyclic a,yS-epoxy ketone 148 into the 5,7,6-tricyclic dolastane skeleton (149) (Scheme 23) [84]. The succeeding hydroxylation of carbon atom by photo oxygenation with singlet oxygen as well as a DIBAH reduction of a keto function proceeded with an undesired substrate-induced diastereoselectivity to provide the racemic 7,14-epimer of the natural dolastane 109. 

The enantioselective ex-chiral-pool synthesis of the enantiomer of the natural (-i-)-dolasta-l(15),7,9-trien-14-ol (ent-122) was achieved by Mehta and coworkers in 1987 (Scheme 24) [85, 86]. From the hydroazulene 136, the synthesis proceeded analogous to the synthesis of Pattenden (Scheme 20) and provided the dolastane ent-122 as a mixture with the non-natural dolas-tanes 153 and 154. However, in contrast to Pattenden s work, Mehta and... 

A B-ring-last-strategy was applied by Majetich and coworkers for their synthesis of the natural ( )-l(15),8-dolastadien-2-ol ( )-107 (desoxyisoami-jiol, 1991) [87, 88]. A Lewis acid mediated intramolecular allylsilane 1,6-ad-dition of the dienone 157 afforded the 5,7,6-tricyclic carbon framework of the dolastanes (158) (Scheme 25). The missing carbon atom was intro-... 

The apparently latest total synthesis of a dolastane diterpene was published by Williams and coworkers in 1993 as a short communication (Fig. 16) [91]. (-)-Clavulara-l(15),17-dien-3,4-diol (129) was synthesized using a strategy that relied on the availability of the enantiomerically pure building block 162 from (+)-9,10-dibromocamphor (163) (Fig. 16). Cornerstones of the synthesis are a macrocyclization that afforded the 11-membered (A+B)C-ring (160) and a transannular cyclization that converted a bicyclic into a tricyclic ring system. Two of the seven chirality centres in the synthetic clavu-... 

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