*2,6-Anhydro-5-deoxy-7-O-benzoyl-4-O-(tert-butyldimethylsilyl)-1,3:8,9:11,12-tri-O-isopropylidene-*β*-*d*manno-*d*-lyxo-dodeco-6-enitol (***4b***)*

A solution of **3** (930 mg, 1.67 mmol) and DMAP (41 mg, 0.333 mmol) in pyridine (15 mL) was treated with benzoyl chloride (1.92 mL, 16.7 mmol) at 0 ◦C. After stirring for 48 h at ambient temperature TLC indicated complete transformation of the starting material and the reaction mixture was diluted with ethyl acetate (60 mL). The organic layer was washed with 1 N hydrochloric acid (3 × 30 mL), sat. aq. NaHCO3-solution (3 × 20 mL) and brine (1 × 20 mL). The solution was dried with Na2SO4, the solvent was removed and the crude product was purified by column chromatography (toluene/ethyl acetate, gradient: 100:1 – 20:1) to afford **4b** (749 mg, 1.13 mmol, 68%) as a colorless crystalline solid. Rf = 0.66 (toluene/ethyl acetate 4:1). [α]20D = +57.1(c = 1.0, CHCl3). M.p. 58 ◦C. 1H-NMR (400 MHz, CDCl3): δ(ppm) = 7.90–8.02 (m, 2H, Ph), 7.52–7.62 (m, 1H, Ph), 7.39–7.48 (m, 2H, Ph), 5.11 (d, *J*5,4 = 2.3 Hz, 1H, H-5), 4.90–5.01 (m, 2H, H-8, H-9), 4.47 (ddd, *J* = 8.2 Hz, *J* = 6.0 Hz, *J*11,12b = 4.0 Hz, 1H, H-11), 4.41 (dd, *J*4,3 = 6.7 Hz, *J*4,5 = 2.2 Hz, 1H, H-4), 4.08–4.17 (m, 2H, H-10, H-12a), 4.05 (dd, *J*12b,12a = 9.1 Hz, *J*12b,11 = 4.0 Hz, 1H, H-12b), 3.66–3.84 (m, 4H, H-1a, H-1b, H-2, H-3), 1.52, 1.48, 1.42, 1.38, 1.37 (5s, 18H, C(C*H*3)2), 0.86 (s, 9H, SiC(C*H*3)3), 0.06, 0.06 (2s, 6H, SiC*H*3).13C-NMR (101 MHz, CDCl3): δ(ppm) = 164.0 (CO), 147.3 (C-6), 133.4, 130.2, 129.9, 128.5 (Ph), 114.2, 109.6 (*C*(CH3)2), 108.2 (C-7), 105.1 (C-5), 99.5 (*C*(CH3)2), 86.7 (C-8), 81.8 (C-10), 80.0 (C-9), 73.3 (C-3), 73.0 (C-11), 70.4 (C-2), 68.5 (C-4), 67.3 (C-12), 61.8 (C-1), 29.1, 27.1, 26.0 (C(*C*H3)2), 25.8 (SiC(*C*H3)3), 25.4, 25.3, 19.3 (C(*C*H3)2), 18.2 (Si*C*(CH3)3), –4.2, –4.7 (Si*C*H3). HRESIMS *m*/*z* 685.30154 (calcd for C34H50O11SiNa, 685.30146); anal. C 61.26, H 8.02, calcd for C34H50O11Si, C 61.61, H 7.60.

#### *General Procedure A for Desilylation of* **4a** *and* **4b**

Tetra-*n*-butylammonium fluoride (1.0 M in THF, 1.5 eq.) was added to a solution of **4a** or **4b** (1.0 mmol) in THF (10 mL) at 0 ◦C. The reaction mixture was warmed to room temperature and stirring was continued until complete conversion of the starting material was detected by TLC. Subsequently, the solution was diluted with CH2Cl2 (20 mL) and washed with brine (3 × 10 mL). The aqueous phase was extracted with CH2Cl2 (2 × 20 mL) and the combined organic phases were dried with Na2SO4. The solvent was evaporated and the residue was purified by column chromatography (petroleum ether/ethyl acetate 2:1 containing 0.5% Et3N).

## *2,6-Anhydro-5-deoxy-7-O-acetyl-1,3:8,9:11,12-tri-O-isopropylidene-*β*-*d*-manno-*d*-lyxo-dodeco-6-enitol (***5a***)*

Following general procedure A **5a** was obtained as a white amorphous solid and was prepared from **4a** in 71% yield stirring the reaction mixture for 20 h. Rf = 0.28 (petroleum ether/ethyl acetate 1:1). [α]20D = +98.0 (c = 1.0, CHCl3). M.p. 179 ◦C (*n*-hexane/ethyl acetate). 1H-NMR (400 MHz, CDCl3): δ(ppm) = 5.14 (d, *J*5,6 = 2.2 Hz, 1H, H-5), 4.88 (dd, *J*9,8 = 5.7 Hz, *J*9,10 = 3.5 Hz, 1H, H-9), 4.71 (d, *J*8,9 = 5.7 Hz, 1H, H-8), 4.37–4.45 (m, 2H, H-4, H-11), 4.01–4.12 (m, 3H, H-10, H-12a, H-12b), 3.85–3.94 (m, 2H, H-1a, H-1b), 3.68–3.80 (m, 2H, H-2, H-3), 2.02 (s, 3H, COC*H*3), 1.53, 1.47, 1.45, 1.42, 1.37, 1.33 (6s, 18H, C(C*H*3)2). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 168.2 (CO), 148.0 (C-6), 113.7, 109.4 (*C*(CH3)2), 107.1 (C-7), 102.9 (C-5), 99.7 (*C*(CH3)2), 86.3 (C-8), 81.5 (C-10), 79.6 (C-9), 73.2 (C-3), 72.8 (C-11), 69.9 (C-2), 67.8 (C-4), 67.0 (C-12), 61.5 (C-1), 28.9, 27.0, 25.8, 25.1, 24.9 (C(*C*H3)2), 21.6 (CO*C*H3), 19.2 (C(*C*H3)2). HRESIMS *m*/*z* 509.19928 (calcd for C23H34O11Na, 509.19933); anal. C 56.57, H 7.17, calcd for C23H34O11, C 56.78, H 7.04.

## *2,6-Anhydro-5-deoxy-7-O-benzoyl-1,3:8,9:11,12-tri-O-isopropylidene-*β*-*d*-manno-*d*-lyxo-dodeco-6-enitol (***5b***)*

Following general procedure A **5b** was obtained as a colorless amorphous solid and was prepared from **4b** in 89% yield stirring the reaction mixture for 24 h. Rf = 0.37 (petroleum ether/ethyl acetate 1:1).

[α]<sup>20</sup> D = +89.4 (c = 1.0, CHCl3). 1H-NMR (400 MHz, CDCl3): δ(ppm) = 7.92–7.99 (m, 2H, Ph), 7.54–7.60 (m, 1H, Ph), 7.41–7.47 (m, 2H, Ph), 5.26 (d, *J*5,4 = 2.2 Hz, 1H, H-5), 4.99 (dd, *J*9,8 = 5.9 Hz, *J*9,10 = 3.6 Hz, 1H, H-9), 4.95 (d, *J*8,9 = 5.9 Hz, 1H, H-8), 4.41–4.50 (m, 2H, H-4, H-11), 4.09–4.14 (m, 2H, H-10, H-12a), 4.04 (dd, *J* = 9.1 Hz, *J* = 4.2 Hz, 1H, H-12b), 3.72–3.88 (m, 4H, H-1a, H-1b, H-2, H-3), 2.11 (br. s., 1H, OH), 1.53, 1.52, 1.42, 1.41, 1.38, 1.36 (6 s, 18H, C(C *H*3)2).13C-NMR (101 MHz, CDCl3): δ(ppm) = 163.9 (CO), 148.4 (C-6), 133.5, 130.1, 129.9, 128.6 (Ph), 114.0, 109.6 ( *C*(CH3)2), 107.9 (C-7), 103.2 (C-5), 99.9 (*C*(CH3)2), 86.6 (C-8), 82.0 (C-10), 79.9 (C-9), 73.4 (C-3), 73.0 (C-11), 70.2 (C-2), 68.1 (C-4), 67.2 (C-12), 61.6 (C-1), 29.1, 27.1, 26.0, 25.2, 25.1, 19.4 (C( *C* H3)2). HRESIMS *m*/*z* 571.21543 (calcd for C28 H36 O11Na, 571.21498); anal. C 61.18, H 6.77, calcd for C28 H36 O11, C 61.30, H 6.61.

#### *General Procedure B for Epoxidation of* **5a** *and* **5b** *and Further Rearrangement to the Oxetanes*

To a solution of *m*CPBA (2.5 eq.) in CH2Cl2 (10 mL) was added potassium fluoride (5 eq.) and the resulting suspension was stirred for 30 min at ambient temperature. A solution containing **5a** or **5b** (0.5 mmol) in CH2Cl2 (10 mL) was added in one portion and stirring was continued for 2 h (epoxidation). To enforce the rearrangemen<sup>t</sup> to the oxetanes the reaction mixture was stirred for 20 h, the white precipitate was filtered o ff and the solution was stirred for further 20 h. The reaction was quenched by addition of sat. aq. NaHCO3-solution (10 mL) and sat. aq. Na2S2O3-solution (10 mL). Subsequently, the aqueous layer was extracted by CH2Cl2 (3 × 10 mL), the combined organic layers were dried with Na2SO4, the solvent was removed and the crude product was purified by column chromatography.

## *5,6-Anhydro-7-O-acetyl-1,3:8,9:11,12-tri-O-isopropylidene-*β*-*d*-manno-*β*-*<sup>d</sup>*-manno-dodeco-6,7-diulo-2,6- pyranose-7,10-furanose (***6a***)*

Following general procedure B a mixture of **6a** and **7a** (8:1) was obtained after quenching the reaction after 2 h as a white amorphous solid and was prepared from **5a** in 94% yield. A mixture of petroleum ether/ethyl acetate 3:1 containing 0.5% Et3N was used as the eluent for column chromatography. Rf = 0.58 (petroleum ether/ethyl acetate 1:2). 1H-NMR (400 MHz, CDCl3): δ(ppm) = 4.96 (d, *J*8,9 = 6.0 Hz, 1H, H-8), 4.91 (dd, *J*9,8 = 6.0 Hz, *J*9,10 = 3.9 Hz, 1H, H-9), 4.31–4.38 (m, 1H, H-11), 4.20 (dd, *J*10,11 = 6.6 Hz, *J*10,9 = 3.9 Hz, 1H, H-10), 3.85–4.06 (m, 5H, H-1a, H-3, H-4, H-12a, H-12b), 3.77 (dd, *J* = 10.7 Hz, *J* = 10.7 Hz, 1H, H-1b), 3.66 (d, *J*5,4 = 2.4 Hz, 1H, H-5), 3.49 (ddd, *J* = 10.2 Hz, *J* = 10.2 Hz, *J* = 5.7 Hz, 1H, H-2), 2.38 (br. s., 1H, OH), 2.06 (s, 3H, COC *H*3), 1.57, 1.48, 1.42, 1.39, 1.35, 1.33 (6s, 18H, C(C *H*3)2). 13C-NMR (101 MHz, CDCl3): δ(ppm) = 169.2 (CO), 114.2, 109.2 ( *C*(CH3)2), 107.9 (C-7), 99.7 ( *C*(CH3)2), 86.2 (C-8), 85.0 (C-6), 82.9 (C-10), 79.9 (C-9), 73.2 (C-11), 73.0 (C-3), 70.6 (C-2), 69.9 (C-4), 66.4, 61.7 (C-1), 57.3 (C-5), 29.1, 27.0, 25.6, 25.3, 24.6 (C( *C* H3)2), 21.9 (CO *C* H3), 19.3 (C( *C* H3)2). HRESIMS *m*/*z* 525.19448 (calcd for C23 H34 O12Na, 525.19425).

## *5,6-Anhydro-7-O-benzoyl-1,3:8,9:11,12-tri-O-isopropylidene-*β*-*d*-manno-*β*-*<sup>d</sup>*-manno-dodeco-6,7-diulo-2,6- pyranose-7,10-furanose (***6b***)*

Following general procedure B, a mixture of **6b** and **7b** (8:1) was obtained after quenching the reaction after 2 h as a white amorphous solid and was prepared from **5b** in 90% yield. A mixture of petroleum ether/ethyl acetate 3:1 containing 0.5% Et3N was used as the eluent for column chromatography. Rf = 0.64 (petroleum ether/ethyl acetate 1:2). 1H-NMR (400 MHz, CDCl3): δ(ppm) = 7.92–7.99 (m, 2H, Ph), 7.59–7.63 (m, 1H, Ph), 7.45–7.50 (m, 2H, Ph), 5.18 (d, *J*8,9 = 6.0 Hz, 1H, H-8), 5.03 (dd, *J*9,8 = 6.1 Hz, *J*9,10 = 4.0 Hz, 1H, H-9), 4.34–4.41 (m, 1H, H-11), 4.31 (dd, *J*10,11 = 6.6 Hz, *J*10,9 = 3.9 Hz, 1H, H-10), 4.13–4.18 (m, 1H, H-4), 4.03 (dd, *J* = 8.9 Hz, *J* = 6.2 Hz, 1H, H-12a), 3.91–3.99 (m, 2H, H-3, 12b), 3.73–3.83 (m, 3H, H-1a, H-1b, H-5), 3.54 (ddd, *J* = 10.0 Hz, *J* = 10.0 Hz, *J* = 6.0 Hz, 1H, H-2), 2.42 (br. s., 1H, OH), 1.62, 1.48, 1.39, 1.37, 1.34 (5s, 18H, C(C *H*3)2). 13C-NMR (101 MHz, CDCl3): δ(ppm) = 164.7 (CO), 133.8, 129.9, 129.8, 128.8 (Ph), 114.3, 109.2 ( *C*(CH3)2), 108.5 (C-7), 99.7 ( *C*(CH3)2), 86.4 (C-8), 85.3 (C-6), 83.2 (C-10), 80.0 (C-9), 73.2 (C-11), 73.0 (C-3), 70.7 (C-2), 69.9 (C-4), 66.4 (C-12), 61.6 (C-1), 57.4 (C-5), 29.0, 26.9, 25.6, 25.3, 24.6, 19.3 (C( *C* H3)2). HRESIMS *m*/*z* 587.21029 (calcd for C28 H36 O12Na, 587.20990).

## *5,7-Anhydro-6-O-acetyl-1,3:8,9:11,12-tri-O-isopropylidene-*β*-*d*-manno-*β*-*<sup>d</sup>*-manno-dodeco-6,7-diulo-2,6- pyranose-7,10-furanose (***7a***)*

Following general procedure B **7a** was obtained after quenching the reaction after 40 h as a white crystalline solid and was prepared from **5a** in 70% yield. A mixture of petroleum ether/ethyl acetate 2:1 was used as the eluent for column chromatography. Crystals from **7a** were grown by overlaying a saturated solution of **7a** in methylene chloride with *n*-heptane and slowly evaporating the methylene chloride. Rf = 0.51 (petroleum ether/ethyl acetate 1:2). [α]<sup>20</sup> D = +18.5 (c = 1.0, CHCl3). M.p. 151 ◦C (*n*-hexane/ethyl acetate). 1H-NMR (400 MHz, CDCl3): δ(ppm) = 5.04 (d, *J*8,9 = 5.6 Hz, 1H, H-8), 4.96 (d, *J*4,5 = 4.9 Hz, 1H, H-5), 4.70 (dd, *J*9,8 = 5.6 Hz, *J*9,10 = 4.0 Hz, 1H, H-9), 4.37–4.46 (m, 1H, H-11), 4.00–4.13 (m, 3H, H-3, H-12a, H12b), 3.86–3.97 (m, 3H, H-1a, H-4, H-10), 3.80 (dd, *J* = 10.5 Hz, 1H, H-1b), 3.65–3.74 (m, 1H, H-2), 2.14 (d, *J*OH,4 = 9.0 Hz, 1H, OH), 2.10 (s, 3H, COC *H*3), 1.56, 1.55, 1.43, 1.43, 1.39, 1.36 (6s, 18H, C(C *H*3)2). 13C-NMR (101 MHz, CDCl3): δ(ppm) = 169.4 ( *C*O), 114.2 ( *C*(CH3)2), 112.9 (C-7), 109.5, 99.9 ( *C*(CH3)2), 98.3 (C-6), 80.9 (C-5), 80.0 (C-10), 79.1 (C-8), 78.6 (C-9), 73.5 (C-11), 71.6 (C-3), 69.1 (C-2), 68.9 (C-4), 67.1 (C-12), 61.8 (C-1), 29.1, 27.1, 25.9, 25.8, 25.4 (C( *C* H3)2), 21.2 (CO *C* H3), 19.2 (C( *C* H3)2). HRESIMS *m*/*z* 525.19318 (calcd for C23 H34 O12Na, 525.19425); anal. C 55.08, H 7.11, calcd for C23 H34 O12, C 54.97, H 6.82.

## *5,7-Anhydro-6-O-benzoyl-1,3:8,9:11,12-tri-O-isopropylidene-*β*-*d*-manno-*β*-*<sup>d</sup>*-manno-dodeco-6,7-diulo-2,6- pyranose-7,10-furanose (***7b***)*

Following general procedure B **7b** was obtained after quenching the reaction after 40 h as a white amorphous solid and was prepared from **5b** in 63% yield. A mixture of petroleum ether/ethyl acetate 2:1 was used as the eluent for column chromatography. Rf = 0.60 (petroleum ether/ethyl acetate 1:2). [α]<sup>20</sup> D = +15.7 (c = 1.0, CHCl3). 1H-NMR (400 MHz, acetone-d6): δ(ppm) = 8.04–8.10 (m, 2H, Ph), 7.68–7.74 (m, 1H, Ph), 7.53–7.59 (m, 2H, Ph), 5.16 (d, *J*8,9 = 5.6 Hz, 1H, H-8), 5.10 (d, *J*5,4 = 4.5 Hz, 1H, H-5), 4.82 (dd, *J*9,8 = 5.6 Hz, *J*9,10 = 3.7 Hz, 1H, H-9), 4.36 (ddd, *J* = 6.5 Hz, *J* = 6.5 Hz, *J* = 5.1 Hz, 1H, H-11), 4.15–4.26 (m, 2H, H-3, OH), 3.99–4.06 (m, 3H, H-4, H-10, H-12a), 3.80–3.97 (m, 4H, H-1a, H-1b, H-2, H-12b), 1.52, 1.51, 1.37, 1.35, 1.34, 1.28 (6s, 18H, C(C *H*3)2). 13C-NMR (101 MHz, acetone-d6): δ(ppm) = 165.7 (CO), 135.0, 130.8, 130.2, 129.7 (Ph), 114.2 ( *C*(CH3)2), 113.5 (C-7), 109.5, 100.2 ( *C*(CH3)2), 99.5 (C-6), 83.3 (C-5), 80.1 (C-10), 79.6 (C-9), 79.6 (C-8), 74.5 (C-11), 72.1 (C-3), 70.7 (C-2), 69.4 (C-4), 67.1 (C-12), 62.4 (C-1), 29.5, 27.2, 26.3, 26.2, 25.7, 19.3 (C( *C* H3)2). HRESIMS *m*/*z* 587.20977 (calcd for C28 H36 O12Na, 587.20990); anal. C 59.64, H 6.86, calcd for C28 H36 O12, C 59.57, H 6.43.

## *5,7-Anhydro-1,3:8,9:11,12-tri-O-isopropylidene-*β*-*d*-manno-*β*-*<sup>d</sup>*-manno-dodeco-6,7-diulo-2,6-pyranose-7,10- furanose (***8***)*

From **7a**: **7a** (50 mg, 0.10 mmol) was dissolved in methanol (2 mL) and ammonia (7 N in methanol, 280 μL, 1.99 mmol) was added at ambient temperature. TLC indicated complete transformation of the starting material after 5 h and the volatile components were removed. Neat **8** (46 mg, 0.099 mmol, 99%) remained as a white crystalline solid.

From **7b**: **7b** (20 mg, 0.0354 mmol) was dissolved in methanol (1 mL) and ammonia (7 N in methanol, 101 μL, 0.708 mmol) was added at ambient temperature. TLC indicated complete transformation of the starting material after 5 h and the volatile components were removed. Subsequently, the crude product was purified by column chromatography (petroleum ether/ethyl acetate 1:2) and **8** (13 mg, 0.282 mmol, 80%) was isolated as a white crystalline solid.

Rf = 0.32 (petroleum ether/ethyl acetate 1:3). [α]<sup>20</sup> D = +17.5 (c = 1.0, CHCl3). M.p. 122 ◦C (*n*-hexane). 1H-NMR (600 MHz, DMSO-*d*6): δ(ppm) = 7.09 (s, 1H, OH-6), 5.16 (d, *J*OH,4 = 5.7 Hz, 1H, OH-4), 4.75 (d, *J*8,9 = 5.9 Hz, 1H, H-8), 4.57–4.63 (m, 2H, H-5, H-9), 4.22 (ddd, *J*11,10 = 7.3 Hz, *J*11,12a = 6.4 Hz, *J*11,12b = 5.1, 1H, H-11), 4.01 (dd, *J*12a,12b = 8.4 Hz, *J*12a,11 = 6.4 Hz, 1H, H-12a), 3.92 (dd, *J*12b,12a = 8.4 Hz, *J*12b,11 = 5.1 Hz, 1H, H-12b), 3.78–3.85 (m, 2H, H-1a, H-3), 3.76 (dd, *J*10,11 = 7.3 Hz, *J*10,9 = 3.7 Hz, 1H, H-10), 3.68 (dd, *J*1b,1a = 10.5 Hz, *J*1b,2 = 10.5 Hz, 1H, H-1b), 3.52 (ddd, *J* = 9.7 Hz, *J*4,OH = 5.1 Hz, *J* = 4.4 Hz, 1H, H-4), 3.40 (ddd, *J*2,1b = 9.9 Hz, *J* = 9.9 Hz, *J* = 5.8 Hz, 1H, H-2), 1.45, 1.39, 1.32, 1.31, 1.28, 1.26 (6s, 18H, C(C*H*3)2).13C-NMR (101 MHz, DMSO-*d*6): δ(ppm) = 112.5 (C-7), 112.3, 108.2, 98.8 (*C*(CH3)2), 97.4 (C-6), 83.9 (C-5), 78.2 (C-9), 77.0 (C-8), 76.9 (C-10), 72.7 (C-11), 71.1 (C-3), 67.8 (C-4), 66.8 (C-2), 66.1 (C-12), 61.1 (C-1), 28.9,26.6, 25.8, 25.5, 25.2, 19.0 (C(*C*H3)2). HRESIMS *m*/*z* 483.18377 (calcd for C21H32O11Na, 483.18368); anal. C 54.58, H 7.41, calcd for C21H32O11, C 54.78, H 7.00.

## **4. Conclusions**

In summary, we have demonstrated that the stability of 2,5-anhydro sugars depends on their chemical environment. In the case of epoxide **6a** and **6b**, where an ester group is adjacent to the epoxide group, reversible rearrangements to highly annulated oxetane-bridged disaccharides **7a** and **7b** occur. In further studies, these compounds serve as precursors for the synthesis of symmetrical dodeco-6,7-diuloses.

**Supplementary Materials:** The following are available online, 1H-NMR and 13C-NMR spectra of all compounds, H,H-NOESY-NMR spectra of compounds **4a** and **4b** and X-ray data of compounds **5a** and **7a**.

**Author Contributions:** Synthesis, conceptualization, investigation, writing—original draft preparation, formal analysis, M.B.; X-ray crystallography, C.M.-M.; conceptualization, investigation, writing—review and editing, validation, supervision, T.Z. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** We thank Petra Schülzle (elemental analysis), Dorothee Wistuba, Claudia Kruse and Peter Haiss (mass spectra) for their contributions to this work.

**Conflicts of Interest:** The authors declare no conflict of interest.
