Subject macrocyclic lactones

To summarize then, procedures for the synthesis of the spiroketal, the side chain, and a simplified southern portion are available. Their joining together to form the macrocyclic lactone present in the mllbemycins and avermectins will be the subject of a future communication. 

The whole family of macrocyclic lactones, consisting of the closely related aver-mectins and milbemycins, displays unprecedented potency against mites, insects, and nematodes. LC90 values in greenhouse trials are often in the range 0.1-0.01 ppm, in some cases even lower. The structure-activity relationships of this chemical class have been the subject of many publications. The present section discusses selected key findings. 

The free radical addition of a thiol to carbon-carbon double or triple bonds is a well-established reaction. It represents one of the most useful methods of synthesizing sulfides under mild conditions. Since its discovery [5] and its much later formulation as a free-radical chain reaction (Scheme 1) [6], the anti-Markovnikov addition of thiols to unsaturated compounds has been the subject of many reviews [8, 9]. These reactions were originally initiated by thermal decomposition of peroxides or azocompounds, by UV irradiation or by radiolysis [10]. (An example of addition of 1-thiosugar to alkenes initiated by 2,2 -azobisisobutyronitrile (AIBN) [11] is reported in equation (1)). More recently, organoboranes have been used as initiators and two examples (Et3B and 9-bora-bicyclo [3.3.1.] nonane) are reported in equations (2) and (3) [12,13]. Troyansky and co-workers [14a] achieved the synthesis of macrocycles like 12- and 13-membered sulfur-containing lactones by the double addition of thiyl radical to alkynes. An example is depicted in equation (4). The same approach has also been applied to the construction of 9- and 18-membered crown thioethers [14b]. The radical chain addition of thiyl radicals to differently substituted allenes has been considered in detail by Paste and co-workers [15], who found that preferential attack occurs at the central allenic carbon and gives rise to a resonance-stabilized ally radical. The addition of benzenethiol to allenic esters has been reported and the product formation has been similarly inferred (equation (5)) [16]. 

---