High Stereochemical Diversity and Applications for the Synthesis of Marine Natural Products: A Library of Carbohydrate Mimics and Polyketide Segments

Abstract

We have developed a powerful concept for the rapid assembly of a series of twenty-four homochiral building blocks from simple racemic trans-2,4-dimethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one. The series comprises eight stereochemical pentades of anomeric [3.3.1]lactone acetals, eight stereochemical tetrades of anomeric carbohydrate mimics, and eight stereotetrades of acyclic polypropionate units. The utility of these enantiopure materials (average 94% ee) in natural product synthesis is demonstrated and shown to complement the popular aldol method.

Stereoselective cyclopropanation of serine- and threonine-derived oxazines to access new morpholine-based scaffolds

“…The reaction was then gently warmed to room temperature and stirred for 16 h. The mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography (hexanes-EtOAc 3 : 1) to yield the cyclopropanated products. , 1 H, H-3), 3.78 (s, 2 H, CO 2 CH 3 a), 3.67 (s, 1 H, CO 2 CH 3 b), 3.54-3.49 (m, 1 H, H-6), 2.00 (t, J = 3.2 Hz, 1 H, H-7), 1.98 (t, J = 7.2 Hz, 2 H, CO 2 CH 2 CH 3 ); d C (50 MHz, CDCl 3 ) mixture of rotamers 169.4 (s, CO 2 ), 169.2 (s, CO 2 ), 155.9 (s, NCO 2 ), 135.7 (s, i-Ph), 128.2-127.1 (d,5 C,Ph), 67.8 and 67.7 (t, CH 2 Ph), 64.6 and 64.1 (t, C-3), 60.7 (t, CO 2 CH 2 CH 3 ), 59.1 (d, C-1) 135.6 (s,5 C,Ph),81.0 [s,C(CH 3 ) 3 ], 67.8 (t, CH 2 Ph), 64.5 and 64.1 (t, C-3), 58.8 (d, C-1), 53.1 (d, C-4), 52.6 (d, C-6) 52.1 (q, CO 2 CH 3 ), 33.5 (d, C-7), 28.0 and 27.4 [q,3 C,C(CH 3 626 mg (2.24 mmol) of compound (S)-5 were treated according to general procedure A using 4.5 equivalents of ethyl diazoacetate (6 h time of addition) to yield 512 mg (63%) of 15a. (Found: C,60.1;H,5.11;N,3.62.…”

“…(Found: C,60.1;H,5.11;N,3.62. C 18 H 21 NO 7 requires C,59.50;H,5.83;N,3.85%); [a] 4 H,CO 2 CH 2 CH 3 ,3.84 (dd,J = 11.6,3.6 Hz,0.6 H,3.80 (dd,J = 11.6,3.6 Hz,0.4 H, (d,5 C,Ph), 67.7 and 67.6 (t, CH 2 Ph), 65.9 and 65.5 (t, C-3), 60.6 (t, CO 2 CH 2 CH 3 ), 58.1 and 57.8 (d, C-1), 55.4 and 54.9 (d, C-4), 52.6 (q, CO 2 CH 3 ), 35.3 and 35.2 (d, C-6), 27.5 and 27.3 (d, C-7) Found: C,61.31;H,6.34;N,3.49. C 20 H 25 NO 7 requires C,61.37;H,6.44 To a solution of dihydroxazine 13 (450 mg, 1.54 mmol) in dry CH 2 Cl 2 (4 mL) cooled in an ice-salt bath were added Cu(OTf) 2 (14 mg, 0.038 mmol), (S,S)-2,2 -isopropylidene-bis(4-t-butyl-2-oxazoline) (11 mg, 0.038 mmol) and phenylhydrazine (3.0 lL, 0.031 mmol).…”

“…The reaction was then gently warmed to room temperature and stirred 16 h. The mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography (hexanes- (d, C-3), 67.6 (t, CH 2 Ph), 58. 8 and 58.4 (d, C-1), 52.7 (q, CO 2 CH 3 ), 52.3 (d, C-4), 34.9 and 34.7 (d,27.9 and 27.6 [q,3 C,C(CH 3 ) 3 ], 27.5 (d, C-7), 17.8 (q,CHCH 3 Compound 15b (240 mg, 0.61 mmol) was dissolved in CH 2 Cl 2 (2.8 mL) and TIS (125 lL, 0.61 mmol) and TFA (1.2 mL) were added sequentially. The mixture was stirred for 50 minutes at room temperature and then the solvents were removed under reduced pressure.…”

The Total Synthesis of C-Glycosides with Completely Resolved Seven-Carbon Backbone Polyol Stereochemistry: Stereochemical Correlations and Access toL-Configured and Other Rare Carbohydrates

“…Furthermore, parallel chemistry has created high-quality polyketide segments which are individually separable. [38] The present strategy is concise and yet can be relied on to fashion a wide range of C-glycosides. Only two oxabicyclics have been used as seven-carbon polyol building blocks.…”

“…After oxidative cleavage either one silylated hydroxy ester [step v(1)] or the constitutional isomer [step v(2)] with interchanged ester and hydroxy functionality have been prepared. [38,40] The synthesis of d-d and of the much less common l-l configured C-glycosides of the third series requires a single inversion at C6 or C2. We have shown previously that [3.3.1]lactone acetals as a new class of compounds are excellent glycosyl donors.…”