An Efficient, Modular Approach for the Synthesis of (+)-Strictifolione and a Related Natural Product

Abstract

An efficient, library amenable, “pot economical” total synthesis of (+)-strictifolione and the related natural product, (6R)-6[(E,4R,6R)-4,6-dihydroxy-10-phenyl-1-decenyl]-5,6-dihydro-2H-2-pyrone are reported. This modular approach takes advantage of two consecutive phosphate tether-mediated, one-pot, sequential protocols, followed by a final cross metathesis to deliver both antifungal natural products in a three-pot process from the respective enantiomeric (R,R)- and (S,S)-trienes with minimal purification. A salient feature of this route is that additional protecting groups are not required as a result of the orthogonal protecting- and leaving-group properties innate to phosphate triesters.

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…292, Scheme 12) from cyclic phosphate triene (e.g. 291) in a one-pot RCM, cross metathesis (with cis stilbene), and diimide hydrogenation sequence was employed in total synthesis of strictifolione (295) and a similar natural product [739]. After transformation of bicyclic phosphate 292 to the diol-alkene 293, cross metathesis with vinyldihydropyran derivative 294 afforded the natural product 295.…”

Phosphate tether-mediated ring-closing metathesis for the generation of medium to large, P-stereogenic bicyclo[n.3.1]phosphates

“…Over the past decade, our group has utilized phosphate triesters as temporary tethers to desymmetrize a number of 1,3- anti -diol-containing dienes via ring-closing metathesis (RCM). 9 Focused on the chemistry of the bicyclo[4.3.1]phosphate, 10 this method served as the cornerstone in the synthesis en route to several natural products, including dolabelide C, 11 salicylihalimide A (formal synthesis), 12 (−)-tetrahydrolipstatin, 13 (+)-strictifolione, 14 and lyngbouilloside. 15 In 2013, we reported 16 a detailed study of the effects of ring size and stereochemical complexity in the phosphate tether-mediated desymmetrization of C 2 -symmetric 1,3- anti diol dienes 17 via RCM reaction to form P -stereogenic 18 , 19 bicyclo[4.3.1]-, bicyclo[5.3.1]-, 20 and bicyclo[7.3.1]phosphates 21 (Figure 1).…”

Synthetic studies to lyngbouilloside: a phosphate tether-mediated synthesis of the macrolactone core

“…In this regard, confirmation of the complete stereostructure of 1 is still unknown, warranting continued effort for its total synthesis. Recently, we have engaged in the synthesis of biologically active natural products using phosphate tether-mediated approaches, 8,9 and have developed a one-pot, sequential RCM/CM/chemoselective hydrogenation protocol mediated by a phosphate tether for the synthesis of advanced polyol and polyketide synthons. 8c Herein, we report application of a one-pot, sequential RCM/CM/chemoselective hydrogenation for the concise synthesis of the originally assigned macrolactone core of (−)-lyngbouilloside, with easy adaptability to C10/C11 and C13 diastereomeric analogs.…”

“…Triene ( R , R )- 5 is readily prepared in 2-steps via sequential tripodal coupling of the C 2 -symmetric anti -diene diol ( R , R )- 7 and allyl alcohol with POCl 3 or in one step utilizing phosphoramidite chemistry. 9a Fragment 6 is obtainable by Brown anti- crotylation and Sharpless asymmetric epoxidation of commercially inexpensive geraniol ( 8 ) in a scalable 9-step route (Scheme 1). …”