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Synthesis 2003(3): 0365-0370
DOI: 10.1055/s-2003-37345
PAPER
© Georg Thieme Verlag Stuttgart · New York

1,4-Dioxamacrolides: Preparation and Sensory Properties

Marcus Eh*
Haarmann & Reimer GmbH, 37603 Holzminden, Germany
Fax: +49(553)1903628; e-Mail: marcus.eh.me@hr-gmbh.de;
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Publikationsverlauf

Received 29 August 2002
Publikationsdatum:
19. Februar 2003 (online)

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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

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