Abstract
The synthesis of 3-methyl-1,4-dioxacylopentadecan-2-one (12c) and 3-methyl-1,4-dioxacylohexadecan-2-one
(12d), two new musk odorants, is described
starting from methyl 2-bromopropionic acid (6b)
and allylic alcohol, respectively. The key step of the synthesis
is the ring-closing olefin metathesis (RCM) to the unsaturated 1,4-dioxamacrolides.
Insight into the structure-odor relationship (SOR) is provided
by the synthesis of ten related unsubstituted or methyl substituted
oxamacrolides. Finally, a four step enantioselective synthesis of
both (3R)-(+)- and (3S)-(-)-3-methyl-1,4-dioxacyclopentadecan-2-one
as well as (3R)-(+)- and (3S)-(-)-3-methyl-1,4-dioxacyclohexadecan-2-one
reveals that mainly the (3R)-(+)
enantiomers are responsible for the powerful musky odor characteristic.
Their synthesis starts from ethyl (2S)-2-hydroxypropanoate
(14) or isobutyl (2R)-2-hydroxypropanoate (15) which were treated under acidic conditions
with allyl trichloroacetimidate (16), followed
by titanate mediated transesterification, ring-closing olefin metathesis
and hydrogenation.
Key words
macrocycles - metathesis - lactones - ring
closure - musk odorants - fragrance - structure-odor
relationship
